1057:
foreign substances into the DNA double helix, or any abnormal changes in DNA tertiary structure that can cause either the loss of DNA, or the misexpression of genes. It appears that H19 expression is tightly linked to the ploidy of the cell. Diploid liver cells express high levels of H19, whereas the polyploid cell fraction do not express H19. Also, diploid mesenchymal stem cells express high levels of H19 compared to polyploid mesenchymal stem cells. Knock-down of H19 lead to increased polyploidization of mesenchymal stem cells, and induced polyploidy resulted in reduced expression of H19, providing a direct link between H19 expression and the amount of DNA within the cell.
901:
with Azad. As well, in a mouse bladder carcinoma cell line, where transfection of a human H19 DNA construct results in high expression of H19, the methylation of the H19 promoter reduces H19 expression. The paternal H19 allele, which is silent postnatally, shows increasing methylation of CpGs in its promoter with gestation time in the fetus. It appears conclusive that the H19 gene is epigenetically controlled via methylation, where methylation on or near the vicinity of one allele prevents the expression of that allele. As well, based on the results from Banet
2833:
109:
134:
342:
140:
1453:(DT-A), is undergoing clinical testing as a treatment for superficial bladder cancer, ovarian cancer and pancreatic cancer. The plasmid, designated BC-819 (or DTA-H19), embodies a targeted therapy approach, in that the plasmid enters all dividing cells, but the DT-A expression is triggered by the presence of H19 transcription factors found only in tumor cells, thus destroying the tumor without affecting normal cells.
1461:
The ovarian cancer patient experienced a 50% decline in the amount of the ovarian cancer marker protein CA-125 in her blood as well as a significant decrease in the number of cancerous cells in her ascitic fluid. The patient suffering from metastatic liver cancer was treated with direct injection of BC-819 into the tumor, with considerable tumor necrosis observed.
1470:
quantities. This knowledge can lead to a more personalized cancer treatment plan; for example, the expression of p95 in a H19-overexpressing cancer cell may indicate higher tolerance of drug toxicity, so cancer treatment for an individual with high levels of H19 (and p95) may focus more on radiotherapy or immunotherapy instead of chemotherapy.
1110:, in contrast to adrenal carcinomas, have upregulated H19 and downregulated IGF2 expression. The upregulated H19 expression, however, came from alleles that were fully methylated. Surgically removed choriocarcinomas from human patients also exhibited a heavily methylated H19 promoter with enhanced H19 expression. This led researchers Arima
1419:
deleted paternal IGF2 gene displayed somatic undergrowth when compared to wildtype mice. This indicates that the loss of H19 is not lethal, H19 expression governs IGF2 repression, and the overexpression of IGF2 is responsible for the overgrowth phenotype observed in the maternal inheritance of a deleted H19 gene.
1095:
transcription. Another point of interest is the significant difference in CpG methylation at site 11 between normal and hyperplasia adrenals. The mean percent CpG methylation at site 11 for hyperplasia and adenoma adrenals is significantly different from that of normal adrenals and carcinoma adrenals, leading Gao
1456:
In a double-center, dose escalation Phase I/IIa clinical trial of BC-819 as a treatment for superficial bladder cancer, no severe adverse events related to the plasmid were detected, and tumor responses were observed in more than 70% of patients, including those with a still not-optimized therapeutic
1251:
H19 is overexpressed in laryngeal squamous cell carcinomas that relapse as compared to those that do not relapse. In a pilot study aimed at the development of a prognostic classifier for this cancer H19 was the strongest predictor of relapse. It was overexpressed in cancers that later developed local
892:
H19 contains a differentially methylated region that is also an imprinting control region. This imprinting control region is differentially methylated at its CpGs according to parental inheritance. Usually, the paternal copy of H19 is methylated and silent while the maternal copy is hypomethylated or
1303:
is a competitive binder of the estrogen receptor and is often used in chemotherapy treatment of breast cancer. While 17-Ξ²-estradiol alone stimulated H19 transcription in MCF-7 cells, the addition of tamoxifen inhibited H19 transcription, demonstrating that there is a putative role of hormones in H19
1150:
investigated various polymorphisms in the H19 gene and found that some heterozygous SNP polymorphisms, such as rs2839698 TC, were associated with a decreased risk of developing non-muscle invasive bladder cancer as well as bladder cancer overall; however, this association disappeared for homozygotes
1073:
in the H19 promoter in normal, hyperplasia, adenoma and carcinoma adrenals. They found that in carcinomas, there was more methylation of CpGs than in normal, hyperplasia and adenoma adrenals. Consequently, normal H19 expression was detectable in normal and hyperplasia adrenals, but in carcinomas and
888:
Within a pregnancy, the father wants the mother to devote as much of her resources as possible towards the growth (benefit) of his offspring. However, within the same pregnancy, the mother wants to conserve as much of her resources as possible towards future births without compromising the health of
1460:
BC-819 was previously tested in human compassionate use for the treatment of superficial bladder cancer, ovarian cancer and metastatic liver cancer. The bladder cancer patient, who was a candidate for radical cystectomy when he was treated in 2004, reported no cancer recurrence and no side effects.
1418:
It is of interest to note that mice inheriting a deleted maternal H19 and a deleted paternal IGF2 gene were indistinguishable from wildtype mice in birth weight and postnatal growth. Mice inheriting only a deleted maternal H19 gene, however, displayed somatic overgrowth while mice inheriting only a
1271:
The exact role of H19 RNA within the cell is currently not known. There are various known substances and conditions that are known to activate H19 transcription and there are various known effects of H19 RNA on cell cycle activity/status, although precisely how H19 RNA exerts these effects is still
1094:
The mean percent methylation of H19 CpGs at sites 13 and 14, after the transcription start site, is insignificant between normal, hyperplasia, adenoma and carcinoma adrenals. This is because methylation of CpGs after the transcription start site is assumed to interfere with RNA polymerase II during
738:
binding sites, however these 3 sites are present in a part of the sequence that has shown no transcriptional activity in deletion assays. As a result, these Sp1 binding sites are not expected to contribute much to the regulation of H19 gene transcription. The H19 gene sequence also contains binding
1414:
found decreased H19 and IGF2 RNA expressions in the gut, liver and kidney; however, the methylation status of these genes were not affected by the deleted enhancer. Suggestions for why H19 is preferentially activated by the 3β enhancer instead of IGF2 are that H19 has a stronger promoter than IGF2
1090:
found that there was not one CpG methylation site that was more important than the others in downregulating H19 expression, they did find that the increase in CpG methylation in adrenal carcinomas followed the pattern of methylation of the normal, hyperplasia and adenoma adrenals. The mean percent
900:
Cells treated with Azad, a demethylating agent, grow much slower than cells cultured in the absence of Azad. At the same time, H19 expression increases while IGF2 expression decreases in the presence of Azad. The reduction of IGF2 expression could be a reason for the slower growth of cells treated
3324:
Coorens THH, Treger TD, Al-Saadi R, Moore L, Tran MGB, Mitchell TJ, Tugnait S, Thevanesan C, Young MD, Oliver TRW, Oostveen M, Collord G, Tarpey PS, Cagan A, Hooks Y, Brougham M, Reynolds BC, Barone G, Anderson J, Jorgensen M, Burke GAA, Visser J, Nicholson JC, Smeulders N, Mushtaq I, Stewart GD,
1436:
The activation of the H19 promoter in cancerous cells (and its silence in normal tissues) has led to the suggestion of using the H19 promoter in gene therapy to drive the expression of cytotoxic genes in tumorigenic cells. Gene therapy trials utilizing the H19 promoter to drive the expression of
1324:
When p57 induction in 0.1% FCS media was measured in the 3 cell lines, both the control and antisense H19 transfected cells had significantly upregulated p57; however, the H19-transfected cells showed a significant downregulation of p57 in 0.1% FCS as compared to 10% FCS. In addition, while the
1056:
Cellular DNA integrity is often compromised in cancer. Genome instability can refer to the accumulation of extra copies of DNA/chromosomes, chromosomal translocations, chromosomal inversion, chromosome deletions, single stranded breaks in DNA, double stranded breaks in DNA, the intercalation of
940:
A common characteristic of imprinted genes is asynchronous replication during the DNA synthesis phase of the mitotic cycle. The replication of two alleles of the same gene can differ according to which parent the allele originated from. On the human chromosome 11p15, the methylated paternal H19
859:
After 10 weeks gestation and in full term placentae, there is exclusive expression of H19 from the maternal chromosome. In the embryo, maternal expression of H19 is present in endodermal and mesodermal tissues. The regulated expression of H19, from biallelic to monoallelic, throughout embryonic
1469:
While the expression profile of H19 in most cancer types is known, the role of H19 RNA in influencing cancer cell response to drug treatment is still unknown. However, recent studies have discovered the expression of thioredoxin and p95 (NCA-90) in cancer cells when H19 RNA is present in high
1077:
The presence of IGF2 RNA expression when H19 RNA was downregulated provides further evidence that IGF2 expression is tightly coupled to and dependent on the absence of H19 expression. As well, the loss of H19 in adrenal cancers may be indicative of tumor suppressor activity by H19, leading Gao
1130:
studies, culturing hepatocellular carcinoma cell lines in hypoxic condition upregulated H19 expression. Whether or not the loss of imprinting for the H19 promoter is a characteristic of hepatocellular carcinoma is not known, as some cell lines exhibit loss of imprinting while others did not.
1410:-null mice, the paternal allele of IGF2 is also silenced as the paternal H19 promoter is no longer methylated and repressed. A reason for the close coupling of H19 and IGF2 expression may be that they share the same 3β gene enhancer. When this 3β enhancer was deleted, researchers Leighton
2457:
1380:
may be potential transcriptional targets of the H19 RNA. As a result of the functions and signaling pathways that H19 RNA-upregulated genes are involved in, it has been suggested that H19 RNA plays crucial roles in tissue invasion, migration and angiogenesis in tumorigenesis.
1037:
Increased H19 expression is found in the following cancers: adrenocortical neoplasms, choriocarcinomas, hepatocellular carcinomas, bladder cancers, ovarian serous epithelial cancers, head and neck carcinomas, endometrial cancer, breast cancer, acute T cell leukemia/lymphoma,
2676:
1321:(normal condition) between the 3 cell lines, when grown in 0.1% FCS (starved serum), the H19-transfected cells maintained their rate of growth while both the control and the antisense H19 transfected cells decreased their rate of proliferation by approximately 50%.
3656:
Sidi AA, Ohana P, Benjamin S, Shalev M, Ransom JH, Lamm D, Hochberg A, Leibovitch I (December 2008). "Phase I/II Marker Lesion Study of
Intravesical BC-819 DNA Plasmid in H19 Over Expressing Superficial Bladder Cancer Refractory to Bacillus Calmette-Guerin".
3325:
Campbell PJ, Wedge DC, Martincorena I, Rampling D, Hook L, Warren AY, Coleman N, Chowdhury T, Sebire N, Drost J, Saeb-Parsy K, Stratton MR, Straathof K, Pritchard-Jones K, Behjati S (2019) Embryonal precursors of Wilms tumor. Science 366(6470):1247-1251
3392:
Lottin S, Vercoutter-Edouart AS, Adriaenssens E, Czeszak X, Lemoine J, Roudbaraki M, Coll J, Hondermarck H, Dugimont T, Curgy JJ (February 2002). "Thioredoxin post-transcriptional regulation by H19 provides a new function to mRNA-like non-coding RNA".
1242:
NCI-H1688, a human lung carcinoma cell line that displays multidrug resistance, also overexpress p95 (NCA-90) and H19. No other cell lines with the multidrug resistance phenotype have been found to overexpress p95 (NCA-90) in conjunction with H19.
714:; the paternal H19 allele is not expressed. H19 was first named ASM (for Adult Skeletal Muscle) because of its expression in adult skeletal muscle ("ASM") in rats. H19 is also known as BWS because aberrant H19 expression can be involved in
1143:, H19 is also upregulated and present in most stages. The presence of H19 RNA was strongest in bladder carcinomas (sampled in situ) that tend to progress rapidly to invasive cancer as well as invasive transitional cell carcinomas.
831:(Insulin Growth Factor 2). Overexpression of IGF2 can be responsible for overgrowth, and generally, IGF2 is expressed in the absence of H19. Mouse embryos overexpressing H19 tend to die between embryonic day 14 and birth. Brunkow
1091:
methylation of H19 CpGs peaked at sites 9 and 10 in normal, hyperplasia, adenoma and carcinoma adrenals and the lowest mean percent methylation of H19 CpGs dipped at site 7 in normal, hyperplasia, adenoma and carcinoma adrenals.
1427:
While the functions of the H19 RNA in the cell are still unclear, its presence in the many types of carcinoma cells suggest that it can be used as a tumor marker for initial diagnosis, cancer recurrence and malignant potential.
57:, BWS, LINC00008, ASM1, NCRNA00008, imprinted maternally expressed transcript, D11S813E, MIR675HG, imprinted maternally expressed transcript (non-protein coding), H19 imprinted maternally expressed transcript, WT2, PRO2605, ASM
1805:
Jinno Y, Ikeda Y, Yun K, Maw M, Masuzaki H, Fukuda H, Inuzuka K, Fujishita A, Ohtani Y, Okimoto T, Ishimaru T, Niikawa N (July 1995). "Establishment of functional imprinting of the H19 gene in human developing placentae".
1316:
promoter, many changes were seen in the resulting cells when compared to both the original T24P cell line and a H19-antisense DNA construct transfected T24P cell line. While there was no difference in proliferation in 10%
3289:
Mirisola V, Mora R, Esposito AI, Guastini L, Tabacchiera F, Paleari L, Amaro A, Angelini G, Dellepiane M, Pfeffer U, Salami A (August 2011). "A prognostic multigene classifier for squamous cell carcinomas of the larynx".
743:
family of transcription factors. One of these C/EBP transcription factor binding sites also contains a CpG site. In vitro methylation of this CpG site on a DNA construct strongly inhibited transcription of the H19 gene.
2636:
Lottin S, Adriaenssens E, Dupressoir T, Berteaux N, Montpellier C, Coll J, Dugimont T, Curgy JJ (November 2002). "Overexpression of an ectopic H19 gene enhances the tumorigenic properties of breast cancer cells".
896:
As methylation of the promoter reaches 100%, H19 expression from that promoter approaches 0. At the same time as H19 expression decreases, the expression of IGF2, a neighboring gene on chromosome 11, increases.
1224:, it was found that MCF-7, a breast adenomacarcinoma cell line, did not express the H19 gene; however a subline of MCF-7 with a multidrug resistance phenotype, MCF-7/AdrVp, had upregulation of H19. Curiously,
1001:
Tumorigenic mesenchymal stem cells express high levels of H19 compared with non-tumorigenic mesenchymal stem cells. Knock-down of H19 in the tumorigenic cells reduced their tumor forming capacity significantly
1252:
or distant recurrence. Its expression did not correlate with the expression of IGF2 and H19 overexpression is unlikely to be a simple consequence of loss of imprinting of the locus containing H19 and IGF2
860:
development suggests that regulation is essential for the growth of embryonic and extraembryonic tissues. Immediately after birth, H19 expression is downregulated in all tissues except for skeletal muscle.
3192:
1392:. Thioredoxin is a protein crucial to the reduction-oxidation reactions involved in metabolism within a cell, and is often found at high levels in cancerous tissues that also overexpress H19 RNA.
1333:, was significantly downregulated in all 3 cell lines, the reduction was approximately 80%-90% in the control and antisense H19 transfected cells and only 30% in the H19 transfected cells.
1694:
Leibovitch MP, Nguyen VC, Gross MS, Solhonne B, Leibovitch SA, Bernheim A (November 1991). "The human ASM (adult skeletal muscle) gene: expression and chromosomal assignment to 11p15".
1201:
have also found that the overexpression of H19 in breast cancer cells promotes proliferation. The expression of H19 in these cells is also independent of the tumor suppressor protein
2936:
el-Naggar AK, Lai S, Tucker SA, Clayman GL, Goepfert H, Hong WK, Huff V (November 1999). "Frequent loss of imprinting at the IGF2 and H19 genes in head and neck squamous carcinoma".
3219:"The 95-kilodalton membrane glycoprotein overexpressed in novel multidrug-resistant breast cancer cells is NCA, the nonspecific cross-reacting antigen of carcinoembryonic antigen"
2901:
Tanos V, Prus D, Ayesh S, Weinstein D, Tykocinski ML, De-Groot N, Hochberg A, Ariel I (July 1999). "Expression of the imprinted H19 oncofetal RNA in epithelial ovarian cancer".
1336:
An examination of the differences in gene expressed between the H19 transfected cells and the antisense H19 transfected cells showed that the following genes were upregulated:
1065:
In contrast to most other cancers, adrenocortical neoplasms appear to have decreased expression of H19. To determine a possible cause for the downregulation of H19, Gao
801:
Free energy (thermodynamics) analysis of the H19 RNA sequence revealed a multitude of possible secondary RNA structures, including 16 helices and various hairpin loops
147:
1232:, a cell membrane efflux pump commonly found in multidrug resistant cells; instead, they overexpress a 95kD membrane glycoprotein p95. p95, or NCA-90, is related to
804:
In situ hybridization of the H19 RNA revealed that it localizes in a cytoplasmic ribonucleoprotein particle, leading some to suggest that the H19 RNA functions as a
3141:"H19 overexpression in breast adenocarcinoma stromal cells is associated with tumor values and steroid receptor status but independent of p53 and Ki-67 expression"
1163:, H19 is expressed. The expression level of H19 RNA in the epithelial cells of the endometrium increases as tissue differentiation is lost in endometrial cancer.
1751:"Methylation loss at H19 imprinted gene correlates with methylenetetrahydrofolate reductase gene promoter hypermethylation in semen samples from infertile males"
1114:
to suggest that in cases of choriocarcinomas, the H19 promoter was mutated, allowing it to overcome the transcriptional repression of promoter CpG methylation.
3478:
Leighton PA, Ingram RS, Eggenschwiler J, Efstratiadis A, Tilghman SM (May 1995). "Disruption of imprinting caused by deletion of the H19 gene region in mice".
3099:
Verhaegh GW, Verkleij L, Vermeulen SH, den Heijer M, Witjes JA, Kiemeney LA (February 2008). "Polymorphisms in the H19 Gene and the Risk of
Bladder Cancer".
1228:
MCF-7/AdrVp cells that lost their multidrug resistance and became drug-sensitive also lost H19 expression. Drug-resistant MCF-AdrVp cells do not overexpress
867:
suggest that the accumulation of H19 RNA in skeletal muscle cells is solely due to the stabilization of that RNA in the muscle cells during differentiation.
3064:
Ariel I, Lustig O, Schneider T, Pizov G, Sappir M, De-Groot N, Hochberg A (February 1995). "The imprinted H19 gene as a tumor marker in bladder carcinoma".
945:
have determined that the later-replicating maternal H19 allele is CTCF-bound, and that it is this CTCF binding that determines the time of H19 replication.
1852:
Kopf E, Bibi O, Ayesh S, et al. (August 1998). "The effect of retinoic acid on the activation of the human H19 promoter by a 3' downstream region".
406:
1400:
H19 and IGF2 expression are closely linked, as they are expressed in the same tissues during fetal development, albeit from differing parental alleles.
1312:
When a cancer bladder cell line, T24P, which does not express H19 was transfected with a DNA construct expressing the H19 gene under the control of the
977:
Tumors formed by injection of bladder carcinoma cells into mice express H19; prior to the injection, these bladder carcinoma cells did not express H19.
2849:
Ariel I, Ayesh S, Perlman EJ, Pizov G, Tanos V, Schneider T, Erdmann VA, Podeh D, Komitowski D, Quasem AS, de Groot N, Hochberg A (February 1997).
2360:
Tanos V, Ariel I, Prus D, De-Groot N, Hochberg A (2004). "H19 and IGF2 gene expression in human normal, hyperplastic, and malignant endometrium".
3344:
Ayesh S, Matouk I, Schneider T, Ohana P, Laster M, Al-Sharef W, De-Groot N, Hochberg A (October 2002). "Possible physiological role of H19 RNA".
1406:
The hypermethylation of the H19 promoter on the paternal allele plays a vital role in allowing the expression of the paternal allele of IGF2. In
3529:
Ariel I, Sughayer M, Fellig Y, Pizov G, Ayesh S, Podeh D, Libdeh BA, Levy C, Birman T, Tykocinski ML, de Groot N, Hochberg A (December 2000).
1515:
998:
The amount of H19 RNA transfected into breast cancer cells did not affect: cell proliferation, cell cycle timing or anchorage-dependent growth
3719:
3026:
Ariel I, de Groot N, Hochberg A (March 2000). "Imprinted H19 gene expression in embryogenesis and human cancer: the oncofetal connection".
987:
3701:
3266:
3249:
1728:
925:
909:
3039:
2458:"Polyploidization of murine mesenchymal cells is associated with suppression of the long noncoding RNA H19 and reduced tumorigenicity"
968:
Cells expressing H19 are able to form bigger colonies in soft agar in anchorage-independent growth assays as compared to the control.
798:
Although the RNA sequence was highly conserved evolutionarily, at the amino acid level, there was a complete absence of conservation
619:
2994:"H19 gene overexpression in atypical multidrug-resistant cells associated with expression of a 95-kilodalton membrane glycoprotein"
1577:
885:
Genomic imprinting is surmised to have arisen due to the conflicting interests of maternal and paternal genes within a pregnancy.
785:
After many studies, researchers finally concluded that the end product of the H19 gene is a RNA strand for the following reasons:
1952:
Berteaux N, Lottin S, MontΓ© D, Pinte S, Quatannens B, Coll J, Hondermarck H, Curgy JJ, Dugimont T, Adriaenssens E (August 2005).
893:
unmethylated and expressed in the offspring cell. Methylation of the H19 promoter is negatively correlated with H19 expression.
870:
In females, H19 is expressed postnatally during puberty and pregnancy in the mammary glands, and in the uterus during pregnancy.
3140:
2256:
Arima T, Matsuda T, Takagi N, Wake N (January 1997). "Association of IGF2 and H19 imprinting with choriocarcinoma development".
2456:
Shoshani O, Massalha H, Shani N, Kagan S, Ravid O, Madar S, Trakhtenbrot L, Leshkowitz D, Rechavi G, Zipori D (December 2012).
1502:
740:
3139:
Adriaenssens E, Dumont L, Lottin S, Bolle D, LeprΓͺtre A, Delobelle A, Bouali F, Dugimont T, Coll J, Curgy JJ (November 1998).
877:
suggests that H19 is continued to be expressed in high amounts in the liver after birth, specifically in diploid hepatocytes.
133:
108:
827:. This has led researchers to suggest that perhaps the only function of H19 RNA expression is to regulate the expression of
1099:
to suggest that site 11 is the initial methylated CpG that eventually leads to widespread methylation of the H19 promoter.
1498:
751:
found that transcription of H19 was under the simultaneous control of both a 5β upstream and a 3β downstream region. Kopf
2308:
Banet G, Bibi O, Matouk I, et al. (September 2000). "Characterization of human and mouse H19 regulatory sequences".
1189:
displayed increased H19 expression when compared to normal breast tissue. Of the tissues with upregulated H19, 92.2% are
2722:
Elkin M, Shevelev A, Schulze E, Tykocinsky M, Cooper M, Ariel I, Pode D, Kopf E, de Groot N, Hochberg A (October 1995).
66:
1074:
surprisingly, adenomas, there was a lower H19 expression that was coupled with detectable (increased) IGF2 expression.
941:
allele replicates early in the S phase while the hypomethylated maternal allele replicates later. Studies by
Bergstrom
824:
715:
1403:
This coupled expression is only lost in cases of loss of imprinting (inherited CpG methylated) or promoter mutation.
839:
The overexpression of H19 in tissues where it is normally expressed (e.g., liver and gut) caused its lethal effects
146:
2677:"The c-Myc oncogene directly induces the H19 noncoding RNA by allele-specific binding to potentiate tumorigenesis"
971:
Downregulation of H19 in breast and lung cancer cells decreases their clonogenicity and anchorage-dependent growth
2158:
795:
The cDNA version of the human H19 does not contain the short introns that are characteristic of imprinted genes
139:
1233:
1123:
856:
In the early placentae (6β8 weeks gestation), both parental H19 alleles (maternal and paternal) are expressed.
735:
707:
3436:
Kim KS, Lee YI (November 1997). "Biallelic expression of the H19 and IGF2 genes in hepatocellular carcinoma".
2561:"Association of H19 promoter methylation with the expression of H19 and IGF-II genes in adrenocortical tumors"
1263:
is a cancer of the kidney that most commonly occurs in childhood. An association with H19 has been reported.
3724:
719:
687:, found in humans and elsewhere. H19 has a role in the negative regulation (or limiting) of body weight and
453:
449:
3579:"Phase 2b, Trial of Intravesical DTA-H19/PEI in Patients With Intermediate-Risk Superficial Bladder Cancer"
2832:
1478:
It is not currently known if H19 expression can be used to induce an anti-cancer response in immune cells.
847:
The expression of H19 in tissues where it is normally not expressed (e.g., brain) caused its lethal effects
1178:
Normal breast tissue does not express H19 RNA, except during puberty and pregnancy in the mammary glands.
2675:
Barsyte-Lovejoy D, Lau SK, Boutros PC, Khosravi F, Jurisica I, Andrulis IL, Tsao MS, Penn LZ (May 2006).
2410:
Adriaenssens E, Lottin S, Dugimont T, Fauquette W, Coll J, Dupouy JP, Boilly B, Curgy JJ (August 1999).
1954:"H19 mRNA-like noncoding RNA promotes breast cancer cell proliferation through positive control by E2F1"
122:
2505:
Moore T, Haig D (February 1991). "Genomic imprinting in mammalian development: a parental tug-of-war".
755:
have suggested that this simultaneous and bidirectional regulation of H19 may involve a member of the
3487:
2793:
756:
22:
3218:
2993:
53:
2117:
722:. Epigenetics deregulations at H19 imprinted gene in sperm have been observed associated with male
2601:
3511:
3418:
3369:
2961:
2753:
2385:
2333:
1929:
1877:
1831:
1676:
1627:
1318:
1160:
1051:
703:
688:
684:
82:
1749:
Rotondo JC, Selvatici R, Di
Domenico M, Marci R, Vesce F, Tognon M, Martini F (September 2013).
792:
There is no known open reading frame; the H19 mRNA contains stop codons in all 3 reading frames
2780:
Matouk IJ, DeGroot N, Mezan S, Ayesh S, Abu-lail R, Hochberg A, Galun E (2007). WΓΆlfl S (ed.).
3682:
3674:
3560:
3503:
3453:
3410:
3361:
3307:
3271:
3230:
3170:
3116:
3081:
3043:
3005:
2953:
2918:
2880:
2821:
2745:
2701:
2654:
2613:
2600:
Hibi K, Nakamura H, Hirai A, Fujikake Y, Kasai Y, Akiyama S, Ito K, Takagi H (February 1996).
2582:
2522:
2482:
2433:
2377:
2325:
2273:
2223:
2139:
2083:
2031:
1975:
1921:
1869:
1823:
1780:
1711:
1668:
1619:
1559:
1341:
1288:
1018:
H19, while possessing oncogenic properties, is best defined as an oncofetal RNA gene because:
983:
c-Myc, an oncogene that functions as a regulator of gene transcription, induces H19 expression
962:
958:
341:
46:
1449:
composed of the H19 gene regulatory sequences that drive the expression of the 'A' strand of
789:
The H19 RNA product is evolutionarily conserved at the nucleotide level in humans and rodents
3666:
3550:
3542:
3495:
3445:
3402:
3353:
3299:
3261:
3160:
3152:
3108:
3073:
3035:
2945:
2910:
2870:
2862:
2811:
2801:
2735:
2691:
2646:
2572:
2514:
2472:
2423:
2369:
2317:
2265:
2213:
2129:
2073:
2065:
2021:
1965:
1911:
1861:
1815:
1770:
1762:
1703:
1658:
1611:
1549:
1450:
1260:
1170:, 75% of low malignancy tumors and 65% of invasive ovarian carcinomas are H19 RNA positive.
1146:
In samples of bladder carcinoma, loss of imprinting at the H19 loci were observed. Verhaugh
1083:
226:
157:
3178:
1295:
were able to individually stimulate H19 transcription in the uterus, while the presence of
1313:
1206:
1194:
1107:
929:
913:
696:
201:
1534:
1039:
78:
3491:
3250:"Decreased sensitivity of carcinoembryonic antigen cDNA-transfected cells to adriamycin"
2797:
1535:"H19 acts as a trans regulator of the imprinted gene network controlling growth in mice"
1139:
Bladder mucosa is one of the tissues that express high levels of H19 RNA prenatally. In
823:
Mice with a loss of H19 function express an overgrowth phenotype similar to babies with
3604:"Phase 1/2a Study of DTA-H19 in Advanced Stage Ovarian Cancer With Symptomatic Ascites"
3555:
3530:
3165:
2816:
2781:
1775:
1750:
1360:, heparin-binding growth factor-like growth factor, intracellular adhesion molecule 1,
1349:
1292:
1229:
1167:
1140:
1082:
to suggest that the loss of H19 and subsequent gain of IGF2 may be involved in adrenal
779:
3449:
3156:
2914:
2875:
2850:
2373:
2269:
2078:
2053:
1865:
1707:
1645:
Rachmilewitz J, Goshen R, Ariel I, Schneider T, de Groot N, Hochberg A (August 1992).
1388:
also found that the overexpression of H19 positively regulates post-transcriptionally
908:
In addition, methylation loss at H19 imprinted gene has been observed associated with
905:, it appears that functional H19 imprinting occurs during early placenta development.
835:
have suggested two reasons for the lethality of H19 overexpression in embryonic mice:
702:
The H19 gene is expressed exclusively on one parental allele in a phenomenon known as
3713:
3077:
2740:
2723:
2518:
1916:
1899:
1663:
1646:
1357:
1182:
805:
774:
The H19 gene codes for a 2.3 kb RNA product. It is transcribed by RNA polymerase II,
3422:
3373:
2757:
2389:
1933:
1881:
1835:
1680:
1631:
1578:"H19: imprinted maternally expressed transcript (non-protein coding) (Homo sapiens)"
1014:
A gene expressed in tumors arising from tissues that express this gene in fetal life
980:
Ectopic H19 expression in vivo enhances the tumorigenic potential of carcinoma cells
3531:"The imprinted H19 gene is a marker of early recurrence in human bladder carcinoma"
3515:
2965:
2337:
1415:
and that the H19 gene is physically closer to the 3β enhancers than the IGF2 gene.
1296:
1284:
on H19 correlated an overexpression of H19 with the presence of steroid receptors.
1190:
1126:, the expression of H19 and IGF2 usually changes from monoallelic to biallelic. In
775:
219:
99:
3628:
3603:
3578:
3248:
Kawaharata H, Hinoda Y, Itoh F, Endo T, Oikawa S, Nakazato H, Imai K (July 1997).
2696:
2477:
762:
H19 gene transcription has also been shown to be activated by the presence of the
3303:
3112:
2806:
812:
Loss of function and overexpression experiments on H19 have revealed two things:
86:
2724:"The expression of the imprinted H19 and IGF-2 genes in human bladder carcinoma"
2650:
2412:"Steroid hormones modulate H19 gene expression in both mammary gland and uterus"
1520:
National Center for
Biotechnology Information, U.S. National Library of Medicine
1389:
917:
723:
3670:
1602:
Zhang Y, Tycko B (April 1992). "Monoallelic expression of the human H19 gene".
2321:
1373:
116:
3678:
1499:
ENSG00000288237 GRCh38: Ensembl release 89: ENSG00000130600, ENSG00000288237
1308:
Downstream effects β angiogenesis, metabolism, tissue invasion and migration
1300:
1225:
370:
319:
240:
185:
172:
74:
3686:
3564:
3414:
3406:
3365:
3311:
3267:
10.1002/(SICI)1097-0215(19970717)72:2<377::AID-IJC29>3.0.CO;2-B
3120:
3047:
2957:
2949:
2922:
2825:
2705:
2658:
2586:
2577:
2560:
2559:
Gao ZH, Suppola S, Liu J, HeikkilΓ€ P, JΓ€nne J, Voutilainen R (March 2002).
2486:
2437:
2428:
2411:
2381:
2329:
2200:
Leighton PA, Saam JR, Ingram RS, Stewart CL, Tilghman SM (September 1995).
2143:
1979:
1970:
1953:
1925:
1784:
1563:
1340:, c-src kinase, tyrosine kinase 2 mitogen-activated protein kinase kinase,
3507:
3457:
3275:
3234:
3174:
3085:
3040:
10.1002/(SICI)1096-8628(20000306)91:1<46::AID-AJMG8>3.0.CO;2-I
3009:
2884:
2749:
2617:
2526:
2277:
2227:
2218:
2201:
2118:"CTCF regulates asynchronous replication of the imprinted H19/Igf2 domain"
2087:
2035:
1873:
1827:
1715:
1672:
1623:
662:
2026:
2009:
1361:
1070:
651:
3546:
2134:
2069:
3217:
Ross DD, Gao Y, Yang W, Leszyk J, Shively J, Doyle LA (December 1997).
2866:
1819:
1554:
1446:
1330:
482:
435:
18:
Negative regulation (or limiting) of body weight and cell proliferation
2166:
2010:"Ectopic expression of the H19 gene in mice causes prenatal lethality"
1766:
1615:
1159:
In normal endometrial tissue, there is no H19 expression; however, in
842:
This implies that H19 gene dosage is under strict control in the fetus
3499:
3357:
711:
692:
632:
392:
3629:"Phase 1/2a DTA-H19 in Patients With Unresentable Pancreatic Cancer"
957:
Overexpression of H19 appears to be important in the development of
500:
496:
1377:
1369:
1365:
1353:
1345:
1217:
6 is sufficient to repress H19 expression in breast cancer cells.
1042:, testicular germ cell cancer, esophageal cancer and lung cancer.
974:
Subcutaneous injection of H19 into mice promoted tumor progression
2116:
BergstrΓΆm R, Whitehead J, Kurukuti S, Ohlsson R (February 2007).
350:
3705:
1732:
1407:
1337:
1326:
1025:
H19 is highly expressed prenatally and downregulated postnatally
921:
828:
763:
680:
70:
1236:, which have been found to reduce drug toxicity by Kawaharata
1214:
1210:
1202:
1185:, 72.5% of the breast adenocarcinomas studied by Adriaenssens
924:-binding site 6 region of H19 can also be hypomethylated with
1898:
Takeuchi S, Hofmann WK, Tsukasaki K, et al. (May 2007).
2782:"The H19 non-coding RNA is essential for human tumor growth"
2052:
Brannan CI, Dees EC, Ingram RS, Tilghman SM (January 1990).
1028:
Postnatally, H19 is expressed at high levels in cancer cells
2851:"The product of the imprinted H19 gene is an oncofetal RNA"
2202:"An enhancer deletion affects both H19 and Igf2 expression"
1900:"Loss of H19 imprinting in adult T-cell leukaemia/lymphoma"
994:
Evidence against the identification of H19 as an oncogene:
2992:
Doyle LA, Yang W, Rishi AK, Gao Y, Ross DD (July 1996).
1329:, required for progression of the cell cycle beyond the
747:
In cell lines derived from human choriocarcinomas, Kopf
209:
953:
Evidence for the identification of H19 as an oncogene:
819:
Overexpression of H19 is a dominant and lethal mutation
691:. This gene also has a role in the formation of some
331:
2054:"The product of the H19 gene may function as an RNA"
1437:
cytotoxic genes are currently being tested on mice.
1209:. However, the presence of tumor suppressor protein
597:
578:
554:
535:
3199:. University of Texas M. D. Anderson Cancer Center
1494:
1492:
1490:
3197:Cancer Biology - Breast Cancer Cell Line Database
3134:
3132:
3130:
156:
3635:. U.S. National Institutes of Health. 2009-11-09
3610:. U.S. National Institutes of Health. 2009-12-03
3585:. U.S. National Institutes of Health. 2009-08-31
3339:
3337:
3335:
3333:
3331:
1584:. National Center for Biotechnology Information
986:Knocking down H19 in hypoxic stress diminishes
3387:
3385:
3383:
2195:
2193:
2191:
2189:
2187:
2185:
2183:
1744:
1742:
1740:
3651:
3649:
3473:
3471:
3469:
3467:
2896:
2894:
2602:"Loss of H19 imprinting in esophageal cancer"
8:
3021:
3019:
2844:
2842:
2111:
2109:
2107:
2105:
2103:
2101:
2099:
2097:
2451:
2449:
2447:
1947:
1945:
1943:
1893:
1891:
1647:"Parental imprinting of the human H19 gene"
1280:A previous study conducted by Adriaenssens
782:, but it does not appear to be translated.
2670:
2668:
2405:
2403:
2401:
2399:
2047:
2045:
2003:
2001:
1999:
1997:
1995:
1993:
1991:
1989:
889:the child(ren) she is currently carrying.
366:
197:
94:
3554:
3265:
3164:
2874:
2815:
2805:
2775:
2773:
2771:
2769:
2767:
2739:
2695:
2631:
2629:
2627:
2576:
2476:
2427:
2217:
2157:Szymanski M, Erdmann VA, Barciszewski J.
2133:
2077:
2025:
1969:
1915:
1774:
1662:
1553:
3059:
3057:
2987:
2985:
2983:
2981:
2979:
2977:
2975:
2717:
2715:
2500:
2498:
2496:
2303:
2301:
2299:
2297:
2295:
2293:
2291:
2289:
2287:
2251:
2249:
2247:
2245:
2243:
2241:
2239:
2237:
1800:
1798:
1796:
1794:
1276:Upstream effectors β hormonal regulation
1022:The final product of the H19 gene is RNA
2159:"Eurekah - Riboregulators: An Overview"
1847:
1845:
1486:
2554:
2552:
2550:
2548:
2546:
2544:
2542:
2540:
2538:
2536:
2355:
2353:
2351:
2349:
2347:
27:
2903:Eur. J. Obstet. Gynecol. Reprod. Biol
2008:Brunkow ME, Tilghman SM (June 1991).
1291:, the dominant form of estrogen, and
161:
120:
115:
7:
3702:Online Mendelian Inheritance in Man
2165:. Landes Bioscience. Archived from
1729:Online Mendelian Inheritance in Man
1267:Participation in signaling pathways
1220:In experiments conducted by Doyle
594:
575:
551:
532:
510:
487:
463:
440:
416:
397:
336:
297:
235:
214:
14:
2374:10.1111/j.1048-891x.2004.014314.x
1010:Definition of an oncofetal gene:
816:Loss of H19 is not lethal in mice
2831:
1917:10.1111/j.1365-2141.2007.06581.x
340:
145:
138:
132:
107:
1069:studied the methylation of 12
710:from the maternally inherited
351:More reference expression data
320:More reference expression data
1:
3450:10.1016/S0304-3835(97)00264-4
3157:10.1016/S0002-9440(10)65748-3
2915:10.1016/S0301-2115(98)00275-9
2697:10.1158/0008-5472.CAN-06-0037
2478:10.1158/0008-5472.CAN-12-1155
2270:10.1016/S0165-4608(96)00221-X
1866:10.1016/S0014-5793(98)00841-2
1708:10.1016/S0006-291X(05)81329-4
1696:Biochem. Biophys. Res. Commun
759:transcription factor family.
130:
3720:Genes on human chromosome 11
3304:10.1016/j.canlet.2011.03.013
3113:10.1016/j.eururo.2008.01.060
3078:10.1016/0090-4295(95)80030-1
2807:10.1371/journal.pone.0000845
2741:10.1016/0014-5793(95)01074-O
2519:10.1016/0168-9525(91)90230-N
1664:10.1016/0014-5793(92)80731-U
1533:Gabory, et al. (2009).
1372:. It is also suggested that
2163:Bioscience Chapter Database
1287:Further studies found that
716:Beckwith-Wiedemann Syndrome
3741:
3671:10.1016/j.juro.2008.08.006
2565:J. Clin. Endocrinol. Metab
1205:and the cell cycle marker
1155:Endometrial/ovarian cancer
1049:
20:
2651:10.1093/carcin/23.11.1885
1516:"Human PubMed Reference:"
1234:carcinoembryonic antigens
1213:and transcription factor
695:and in the regulation of
666:
661:
657:
650:
631:
614:
601:
582:
571:
558:
539:
528:
517:
513:
494:
490:
481:
470:
466:
447:
443:
434:
423:
419:
404:
400:
391:
376:
369:
365:
348:
339:
330:
317:
304:
300:
247:
238:
208:
200:
196:
179:
166:
129:
106:
97:
93:
64:
61:
51:
44:
39:
35:
30:
3193:"Breast Cell Line MCF-7"
1124:hepatocellular carcinoma
1118:Hepatocellular carcinoma
1061:Adrenocortical neoplasms
1006:As an oncofetal RNA gene
734:The H19 gene contains 3
2362:Int. J. Gynecol. Cancer
2322:10.1023/A:1007139713781
2258:Cancer Genet. Cytogenet
1299:inhibited this effect.
720:Silver-Russell syndrome
3659:The Journal of Urology
3407:10.1038/sj.onc.1205233
2950:10.1038/sj.onc.1203192
2578:10.1210/jcem.87.3.8331
2429:10.1038/sj.onc.1202819
1971:10.1074/jbc.M504033200
1197:. Studies by Berteaux
920:males. Similarly, the
916:in semen samples from
766:transcription factor.
275:skeletal muscle tissue
2219:10.1101/gad.9.17.2079
1255:
730:Gene characterization
123:Chromosome 11 (human)
2027:10.1101/gad.5.6.1092
873:A study by Shoshani
718:("BWS"), as well as
267:gastrocnemius muscle
263:right adrenal cortex
23:H19 (disambiguation)
21:For other uses, see
3547:10.1136/mp.53.6.320
3492:1995Natur.375...34L
2798:2007PLoSO...2..845M
2135:10.4161/cc.6.4.3854
2070:10.1128/MCB.10.1.28
1964:(33): 29625β29636.
852:Expression timeline
287:canal of the cervix
271:left adrenal cortex
3633:ClinicalTrials.gov
3608:ClinicalTrials.gov
3583:ClinicalTrials.gov
2867:10.1136/mp.50.1.34
1820:10.1038/ng0795-318
1555:10.1242/dev.036061
1457:dose and regimen.
1193:and only 2.9% are
1161:endometrial cancer
1052:Genome instability
1046:Genome instability
689:cell proliferation
685:long noncoding RNA
3706:H19 Gene - 103280
3401:(10): 1625β1631.
3229:(24): 5460β5464.
3028:Am. J. Med. Genet
3004:(13): 2904β2907.
2944:(50): 7063β7069.
2690:(10): 5330β5337.
2645:(11): 1885β1895.
2471:(24): 6403β6413.
2422:(31): 4460β4473.
2212:(17): 2079β2089.
1767:10.4161/epi.25798
1733:H19 Gene - 103280
1616:10.1038/ng0492-40
1548:(20): 3413β3421.
1342:tyrosine kinase 2
963:colorectal cancer
863:Studies by Tanos
674:
673:
670:
669:
646:
645:
610:
609:
591:
590:
567:
566:
548:
547:
524:
523:
507:
506:
477:
476:
460:
459:
430:
429:
413:
412:
361:
360:
357:
356:
326:
325:
313:
312:
294:
293:
279:left uterine tube
192:
191:
3732:
3691:
3690:
3665:(6): 2379β2383.
3653:
3644:
3643:
3641:
3640:
3625:
3619:
3618:
3616:
3615:
3600:
3594:
3593:
3591:
3590:
3575:
3569:
3568:
3558:
3526:
3520:
3519:
3500:10.1038/375034a0
3475:
3462:
3461:
3433:
3427:
3426:
3389:
3378:
3377:
3358:10.1002/mc.10075
3341:
3326:
3322:
3316:
3315:
3286:
3280:
3279:
3269:
3245:
3239:
3238:
3214:
3208:
3207:
3205:
3204:
3189:
3183:
3182:
3177:. Archived from
3168:
3151:(5): 1597β1607.
3136:
3125:
3124:
3107:(5): 1118β1126.
3096:
3090:
3089:
3061:
3052:
3051:
3023:
3014:
3013:
2989:
2970:
2969:
2933:
2927:
2926:
2898:
2889:
2888:
2878:
2846:
2837:
2836:
2835:
2829:
2819:
2809:
2777:
2762:
2761:
2743:
2719:
2710:
2709:
2699:
2681:
2672:
2663:
2662:
2633:
2622:
2621:
2597:
2591:
2590:
2580:
2571:(3): 1170β1176.
2556:
2531:
2530:
2502:
2491:
2490:
2480:
2462:
2453:
2442:
2441:
2431:
2407:
2394:
2393:
2357:
2342:
2341:
2305:
2282:
2281:
2253:
2232:
2231:
2221:
2197:
2178:
2177:
2175:
2174:
2154:
2148:
2147:
2137:
2113:
2092:
2091:
2081:
2049:
2040:
2039:
2029:
2020:(6): 1092β1101.
2005:
1984:
1983:
1973:
1949:
1938:
1937:
1919:
1895:
1886:
1885:
1849:
1840:
1839:
1802:
1789:
1788:
1778:
1746:
1735:
1726:
1720:
1719:
1702:(3): 1241β1250.
1691:
1685:
1684:
1666:
1642:
1636:
1635:
1599:
1593:
1592:
1590:
1589:
1574:
1568:
1567:
1557:
1539:
1530:
1524:
1523:
1512:
1506:
1496:
1465:Pharmacogenomics
1451:Diphtheria Toxin
1226:mutant revertant
1195:epithelial cells
1108:Choriocarcinomas
1103:Choriocarcinomas
1084:cancer induction
930:hypermethylation
914:hypermethylation
659:
658:
642:
627:
622:
620:Chr 11: 2 β 2 Mb
605:
595:
586:
576:
572:RefSeq (protein)
562:
552:
543:
533:
511:
488:
464:
441:
417:
398:
367:
353:
344:
337:
322:
298:
243:
241:Top expressed in
236:
215:
198:
188:
175:
164:
149:
142:
136:
125:
111:
95:
89:
56:
49:
28:
3740:
3739:
3735:
3734:
3733:
3731:
3730:
3729:
3710:
3709:
3699:
3694:
3655:
3654:
3647:
3638:
3636:
3627:
3626:
3622:
3613:
3611:
3602:
3601:
3597:
3588:
3586:
3577:
3576:
3572:
3528:
3527:
3523:
3486:(6526): 34β39.
3477:
3476:
3465:
3435:
3434:
3430:
3391:
3390:
3381:
3343:
3342:
3329:
3323:
3319:
3288:
3287:
3283:
3247:
3246:
3242:
3216:
3215:
3211:
3202:
3200:
3191:
3190:
3186:
3138:
3137:
3128:
3098:
3097:
3093:
3063:
3062:
3055:
3025:
3024:
3017:
2991:
2990:
2973:
2935:
2934:
2930:
2900:
2899:
2892:
2848:
2847:
2840:
2830:
2779:
2778:
2765:
2721:
2720:
2713:
2679:
2674:
2673:
2666:
2635:
2634:
2625:
2599:
2598:
2594:
2558:
2557:
2534:
2504:
2503:
2494:
2465:Cancer Research
2460:
2455:
2454:
2445:
2409:
2408:
2397:
2359:
2358:
2345:
2307:
2306:
2285:
2255:
2254:
2235:
2199:
2198:
2181:
2172:
2170:
2156:
2155:
2151:
2115:
2114:
2095:
2058:Mol. Cell. Biol
2051:
2050:
2043:
2007:
2006:
1987:
1951:
1950:
1941:
1904:Br. J. Haematol
1897:
1896:
1889:
1851:
1850:
1843:
1804:
1803:
1792:
1748:
1747:
1738:
1727:
1723:
1693:
1692:
1688:
1644:
1643:
1639:
1601:
1600:
1596:
1587:
1585:
1576:
1575:
1571:
1537:
1532:
1531:
1527:
1514:
1513:
1509:
1497:
1488:
1484:
1476:
1467:
1443:
1434:
1425:
1398:
1314:cytomegalovirus
1310:
1304:transcription.
1278:
1269:
1258:
1249:
1176:
1168:ovarian cancers
1157:
1141:bladder cancers
1137:
1135:Bladder cancers
1120:
1105:
1086:. Although Gao
1063:
1054:
1048:
1035:
1008:
951:
938:
883:
854:
772:
732:
697:gene expression
663:View/Edit Human
640:
625:
618:
615:Location (UCSC)
603:
584:
560:
541:
499:
454:ENSG00000288237
452:
450:ENSG00000130600
349:
318:
309:
290:
285:
281:
277:
273:
269:
265:
261:
257:
255:muscle of thigh
253:
239:
183:
170:
162:
152:
151:
150:
143:
121:
98:Gene location (
87:H19 - orthologs
65:
52:
45:
26:
19:
12:
11:
5:
3738:
3736:
3728:
3727:
3725:Non-coding RNA
3722:
3712:
3711:
3698:
3697:External links
3695:
3693:
3692:
3645:
3620:
3595:
3570:
3541:(6): 320β323.
3521:
3463:
3444:(2): 143β148.
3428:
3379:
3327:
3317:
3292:Cancer Letters
3281:
3260:(2): 377β382.
3254:Int. J. Cancer
3240:
3209:
3184:
3181:on 2003-09-12.
3126:
3091:
3072:(2): 335β338.
3053:
3015:
2971:
2928:
2890:
2838:
2763:
2711:
2664:
2639:Carcinogenesis
2623:
2612:(3): 480β482.
2592:
2532:
2492:
2443:
2395:
2368:(3): 521β525.
2343:
2316:(3): 157β165.
2310:Mol. Biol. Rep
2283:
2233:
2179:
2149:
2128:(4): 450β454.
2093:
2041:
1985:
1939:
1910:(4): 380β381.
1887:
1860:(3): 123β127.
1841:
1814:(3): 318β324.
1790:
1761:(9): 990β997.
1736:
1721:
1686:
1637:
1594:
1569:
1525:
1507:
1485:
1483:
1480:
1475:
1472:
1466:
1463:
1442:
1441:Drug discovery
1439:
1433:
1430:
1424:
1423:Cancer therapy
1421:
1397:
1394:
1350:Janus kinase 1
1325:expression of
1309:
1306:
1293:corticosterone
1289:17-Ξ²-estradiol
1277:
1274:
1268:
1265:
1257:
1254:
1248:
1245:
1230:P-glycoprotein
1175:
1172:
1156:
1153:
1136:
1133:
1119:
1116:
1104:
1101:
1062:
1059:
1050:Main article:
1047:
1044:
1034:
1033:Role in cancer
1031:
1030:
1029:
1026:
1023:
1016:
1015:
1007:
1004:
1003:
1002:
999:
992:
991:
984:
981:
978:
975:
972:
969:
966:
950:
949:As an oncogene
947:
937:
934:
928:gene promoter
912:gene promoter
882:
879:
853:
850:
849:
848:
845:
844:
843:
821:
820:
817:
810:
809:
802:
799:
796:
793:
790:
780:polyadenylated
771:
768:
739:sites for the
731:
728:
706:. H19 is only
672:
671:
668:
667:
665:
655:
654:
648:
647:
644:
643:
638:
636:
629:
628:
623:
616:
612:
611:
608:
607:
599:
598:
592:
589:
588:
580:
579:
573:
569:
568:
565:
564:
556:
555:
549:
546:
545:
537:
536:
530:
526:
525:
522:
521:
515:
514:
508:
505:
504:
492:
491:
485:
479:
478:
475:
474:
468:
467:
461:
458:
457:
445:
444:
438:
432:
431:
428:
427:
421:
420:
414:
411:
410:
402:
401:
395:
389:
388:
383:
378:
374:
373:
363:
362:
359:
358:
355:
354:
346:
345:
334:
328:
327:
324:
323:
315:
314:
311:
310:
308:
305:
302:
301:
295:
292:
291:
289:
288:
284:
283:left ventricle
280:
276:
272:
268:
264:
260:
256:
252:
248:
245:
244:
232:
231:
223:
212:
206:
205:
202:RNA expression
194:
193:
190:
189:
181:
177:
176:
168:
165:
160:
154:
153:
144:
137:
131:
127:
126:
119:
113:
112:
104:
103:
91:
90:
63:
59:
58:
50:
42:
41:
37:
36:
33:
32:
17:
13:
10:
9:
6:
4:
3:
2:
3737:
3726:
3723:
3721:
3718:
3717:
3715:
3708:
3707:
3703:
3696:
3688:
3684:
3680:
3676:
3672:
3668:
3664:
3660:
3652:
3650:
3646:
3634:
3630:
3624:
3621:
3609:
3605:
3599:
3596:
3584:
3580:
3574:
3571:
3566:
3562:
3557:
3552:
3548:
3544:
3540:
3536:
3532:
3525:
3522:
3517:
3513:
3509:
3505:
3501:
3497:
3493:
3489:
3485:
3481:
3474:
3472:
3470:
3468:
3464:
3459:
3455:
3451:
3447:
3443:
3439:
3432:
3429:
3424:
3420:
3416:
3412:
3408:
3404:
3400:
3396:
3388:
3386:
3384:
3380:
3375:
3371:
3367:
3363:
3359:
3355:
3351:
3347:
3346:Mol. Carcinog
3340:
3338:
3336:
3334:
3332:
3328:
3321:
3318:
3313:
3309:
3305:
3301:
3297:
3293:
3285:
3282:
3277:
3273:
3268:
3263:
3259:
3255:
3251:
3244:
3241:
3236:
3232:
3228:
3224:
3220:
3213:
3210:
3198:
3194:
3188:
3185:
3180:
3176:
3172:
3167:
3162:
3158:
3154:
3150:
3146:
3145:Am. J. Pathol
3142:
3135:
3133:
3131:
3127:
3122:
3118:
3114:
3110:
3106:
3102:
3095:
3092:
3087:
3083:
3079:
3075:
3071:
3067:
3060:
3058:
3054:
3049:
3045:
3041:
3037:
3033:
3029:
3022:
3020:
3016:
3011:
3007:
3003:
2999:
2995:
2988:
2986:
2984:
2982:
2980:
2978:
2976:
2972:
2967:
2963:
2959:
2955:
2951:
2947:
2943:
2939:
2932:
2929:
2924:
2920:
2916:
2912:
2908:
2904:
2897:
2895:
2891:
2886:
2882:
2877:
2872:
2868:
2864:
2860:
2856:
2852:
2845:
2843:
2839:
2834:
2827:
2823:
2818:
2813:
2808:
2803:
2799:
2795:
2791:
2787:
2783:
2776:
2774:
2772:
2770:
2768:
2764:
2759:
2755:
2751:
2747:
2742:
2737:
2733:
2729:
2725:
2718:
2716:
2712:
2707:
2703:
2698:
2693:
2689:
2685:
2678:
2671:
2669:
2665:
2660:
2656:
2652:
2648:
2644:
2640:
2632:
2630:
2628:
2624:
2619:
2615:
2611:
2607:
2603:
2596:
2593:
2588:
2584:
2579:
2574:
2570:
2566:
2562:
2555:
2553:
2551:
2549:
2547:
2545:
2543:
2541:
2539:
2537:
2533:
2528:
2524:
2520:
2516:
2512:
2508:
2501:
2499:
2497:
2493:
2488:
2484:
2479:
2474:
2470:
2466:
2459:
2452:
2450:
2448:
2444:
2439:
2435:
2430:
2425:
2421:
2417:
2413:
2406:
2404:
2402:
2400:
2396:
2391:
2387:
2383:
2379:
2375:
2371:
2367:
2363:
2356:
2354:
2352:
2350:
2348:
2344:
2339:
2335:
2331:
2327:
2323:
2319:
2315:
2311:
2304:
2302:
2300:
2298:
2296:
2294:
2292:
2290:
2288:
2284:
2279:
2275:
2271:
2267:
2263:
2259:
2252:
2250:
2248:
2246:
2244:
2242:
2240:
2238:
2234:
2229:
2225:
2220:
2215:
2211:
2207:
2203:
2196:
2194:
2192:
2190:
2188:
2186:
2184:
2180:
2169:on 2007-07-06
2168:
2164:
2160:
2153:
2150:
2145:
2141:
2136:
2131:
2127:
2123:
2119:
2112:
2110:
2108:
2106:
2104:
2102:
2100:
2098:
2094:
2089:
2085:
2080:
2075:
2071:
2067:
2063:
2059:
2055:
2048:
2046:
2042:
2037:
2033:
2028:
2023:
2019:
2015:
2011:
2004:
2002:
2000:
1998:
1996:
1994:
1992:
1990:
1986:
1981:
1977:
1972:
1967:
1963:
1959:
1958:J. Biol. Chem
1955:
1948:
1946:
1944:
1940:
1935:
1931:
1927:
1923:
1918:
1913:
1909:
1905:
1901:
1894:
1892:
1888:
1883:
1879:
1875:
1871:
1867:
1863:
1859:
1855:
1848:
1846:
1842:
1837:
1833:
1829:
1825:
1821:
1817:
1813:
1809:
1801:
1799:
1797:
1795:
1791:
1786:
1782:
1777:
1772:
1768:
1764:
1760:
1756:
1752:
1745:
1743:
1741:
1737:
1734:
1730:
1725:
1722:
1717:
1713:
1709:
1705:
1701:
1697:
1690:
1687:
1682:
1678:
1674:
1670:
1665:
1660:
1656:
1652:
1648:
1641:
1638:
1633:
1629:
1625:
1621:
1617:
1613:
1609:
1605:
1598:
1595:
1583:
1579:
1573:
1570:
1565:
1561:
1556:
1551:
1547:
1543:
1536:
1529:
1526:
1521:
1517:
1511:
1508:
1504:
1500:
1495:
1493:
1491:
1487:
1481:
1479:
1474:Immunotherapy
1473:
1471:
1464:
1462:
1458:
1454:
1452:
1448:
1440:
1438:
1431:
1429:
1422:
1420:
1416:
1413:
1409:
1404:
1401:
1395:
1393:
1391:
1387:
1382:
1379:
1375:
1371:
1367:
1363:
1359:
1358:interleukin-6
1355:
1351:
1347:
1343:
1339:
1334:
1332:
1328:
1322:
1320:
1315:
1307:
1305:
1302:
1298:
1294:
1290:
1285:
1283:
1275:
1273:
1266:
1264:
1262:
1261:Wilms' tumour
1256:Wilms' tumour
1253:
1247:Larynx cancer
1246:
1244:
1240:
1239:
1235:
1231:
1227:
1223:
1218:
1216:
1212:
1208:
1204:
1200:
1196:
1192:
1191:stromal cells
1188:
1184:
1183:breast cancer
1179:
1174:Breast cancer
1173:
1171:
1169:
1164:
1162:
1154:
1152:
1149:
1144:
1142:
1134:
1132:
1129:
1125:
1117:
1115:
1113:
1109:
1102:
1100:
1098:
1092:
1089:
1085:
1081:
1075:
1072:
1068:
1060:
1058:
1053:
1045:
1043:
1041:
1032:
1027:
1024:
1021:
1020:
1019:
1013:
1012:
1011:
1005:
1000:
997:
996:
995:
989:
985:
982:
979:
976:
973:
970:
967:
964:
960:
956:
955:
954:
948:
946:
944:
935:
933:
931:
927:
923:
919:
915:
911:
906:
904:
898:
894:
890:
886:
880:
878:
876:
871:
868:
866:
861:
857:
851:
846:
841:
840:
838:
837:
836:
834:
830:
826:
818:
815:
814:
813:
807:
806:riboregulator
803:
800:
797:
794:
791:
788:
787:
786:
783:
781:
777:
769:
767:
765:
760:
758:
754:
750:
745:
742:
737:
729:
727:
725:
721:
717:
713:
709:
705:
700:
698:
694:
690:
686:
682:
678:
664:
660:
656:
653:
649:
639:
637:
634:
630:
624:
621:
617:
613:
606:
600:
596:
593:
587:
581:
577:
574:
570:
563:
557:
553:
550:
544:
538:
534:
531:
529:RefSeq (mRNA)
527:
520:
516:
512:
509:
503:
502:
498:
493:
489:
486:
484:
480:
473:
469:
465:
462:
456:
455:
451:
446:
442:
439:
437:
433:
426:
422:
418:
415:
409:
408:
403:
399:
396:
394:
390:
387:
384:
382:
379:
375:
372:
368:
364:
352:
347:
343:
338:
335:
333:
329:
321:
316:
306:
303:
299:
296:
286:
282:
278:
274:
270:
266:
262:
259:apex of heart
258:
254:
250:
249:
246:
242:
237:
234:
233:
230:
228:
224:
222:
221:
217:
216:
213:
211:
207:
203:
199:
195:
187:
182:
178:
174:
169:
159:
155:
148:
141:
135:
128:
124:
118:
114:
110:
105:
101:
96:
92:
88:
84:
80:
76:
72:
68:
60:
55:
48:
43:
38:
34:
29:
24:
16:
3700:
3662:
3658:
3637:. Retrieved
3632:
3623:
3612:. Retrieved
3607:
3598:
3587:. Retrieved
3582:
3573:
3538:
3534:
3524:
3483:
3479:
3441:
3437:
3431:
3398:
3394:
3352:(2): 63β74.
3349:
3345:
3320:
3298:(1): 37β46.
3295:
3291:
3284:
3257:
3253:
3243:
3226:
3222:
3212:
3201:. Retrieved
3196:
3187:
3179:the original
3148:
3144:
3104:
3100:
3094:
3069:
3065:
3034:(1): 46β50.
3031:
3027:
3001:
2997:
2941:
2937:
2931:
2906:
2902:
2861:(1): 34β44.
2858:
2854:
2789:
2785:
2734:(1): 57β61.
2731:
2727:
2687:
2683:
2642:
2638:
2609:
2605:
2595:
2568:
2564:
2513:(2): 45β49.
2510:
2507:Trends Genet
2506:
2468:
2464:
2419:
2415:
2365:
2361:
2313:
2309:
2264:(1): 39β47.
2261:
2257:
2209:
2205:
2171:. Retrieved
2167:the original
2162:
2152:
2125:
2121:
2064:(1): 28β36.
2061:
2057:
2017:
2013:
1961:
1957:
1907:
1903:
1857:
1853:
1811:
1807:
1758:
1754:
1724:
1699:
1695:
1689:
1657:(1): 25β28.
1654:
1650:
1640:
1610:(1): 40β44.
1607:
1603:
1597:
1586:. Retrieved
1581:
1572:
1545:
1541:
1528:
1519:
1510:
1477:
1468:
1459:
1455:
1444:
1435:
1432:Gene therapy
1426:
1417:
1411:
1405:
1402:
1399:
1385:
1383:
1335:
1323:
1311:
1297:progesterone
1286:
1281:
1279:
1270:
1259:
1250:
1241:
1237:
1221:
1219:
1198:
1186:
1181:However, in
1180:
1177:
1165:
1158:
1147:
1145:
1138:
1127:
1121:
1111:
1106:
1096:
1093:
1087:
1079:
1076:
1066:
1064:
1055:
1040:Wilms' tumor
1036:
1017:
1009:
993:
952:
942:
939:
907:
902:
899:
895:
891:
887:
884:
874:
872:
869:
864:
862:
858:
855:
832:
822:
811:
784:
773:
761:
752:
748:
746:
733:
701:
676:
675:
602:
583:
559:
540:
518:
495:
471:
448:
424:
405:
385:
380:
225:
218:
62:External IDs
15:
3535:Mol. Pathol
3438:Cancer Lett
2909:(1): 7β11.
2855:Mol. Pathol
2792:(9): e845.
1755:Epigenetics
1582:Entrez Gene
1542:Development
1390:thioredoxin
936:Replication
881:Epigenetics
770:RNA product
724:infertility
708:transcribed
40:Identifiers
3714:Categories
3639:2010-01-14
3614:2010-01-14
3589:2010-01-14
3223:Cancer Res
3203:2008-06-06
2998:Cancer Res
2684:Cancer Res
2606:Cancer Res
2173:2008-06-06
2122:Cell Cycle
1808:Nat. Genet
1604:Nat. Genet
1588:2008-06-06
1505:, May 2017
1482:References
1374:angiogenin
959:esophageal
704:imprinting
229:(ortholog)
184:2,001,470
171:1,995,171
3679:0022-5347
3101:Eur. Urol
2728:FEBS Lett
2206:Genes Dev
2014:Genes Dev
1854:FEBS Lett
1651:FEBS Lett
1366:ephrin A4
1348:, JNK1,
1301:Tamoxifen
1272:unknown.
1071:CpG sites
990:induction
918:infertile
371:Orthologs
75:GeneCards
3704:(OMIM):
3687:18950807
3565:11193051
3423:29493356
3415:11896592
3395:Oncogene
3374:38724288
3366:12325036
3312:21481529
3121:18262338
3048:10751088
2958:10597307
2938:Oncogene
2923:10428315
2826:17786216
2786:PLOS ONE
2758:21179965
2706:16707459
2659:12419837
2587:11889182
2487:23047867
2438:10442637
2416:Oncogene
2390:43533877
2382:15228427
2330:11254105
2144:17329968
1980:15985428
1934:46427539
1926:17408396
1882:30015086
1836:34185893
1785:23975186
1731:(OMIM):
1681:22194553
1632:35338859
1564:19762426
1501:–
1128:in vitro
652:Wikidata
251:placenta
3556:1186987
3516:2998931
3508:7536897
3488:Bibcode
3458:9570364
3276:9219849
3235:9407950
3175:9811352
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