Biallelic expression of the H19 and IGF2 genes in hepatocellular carcinoma

Kim, Kyoung-Sook; Lee, Young Ik

doi:10.1016/s0304-3835(97)00264-4

Cited by 64 publications

(45 citation statements)

References 22 publications

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“…H19 is a member of a highly-conserved cluster of imprinted genes, and was the first lncRNA to be associated with cancer (12). Previous studies have indicated that H19 exhibits dysregulated expression in GC (13,14), hepatocellular carcinoma (15), bladder cancer (16), breast cancer (17) and esophageal cancer (18), and that itmay cause tumor promoting and suppressing effects (19). Niu et al (20) screened lncRNA expression profilesfrom colorectal cancer and adenoma samples, and identified a novel lncRNA, AK027294, which was associated with cell proliferation, migration and apoptosis in colorectal cancer cells.…”

Section: Introductionmentioning

confidence: 99%

Downregulated long non‑coding RNA TCONS_00068220 upregulates apoptosis in gastric cancer cells

et al. 2017

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Abstract. Long non-coding RNAs (lncRNAs) are emerging as a fundamental class of biological effect or molecules that perform pivotal functions in the regulation of the genome. With advances in bioinformatics and genomics, extensive identification and characterization of lncRNAs is now possible. They regulate cellular growth, differentiation and apoptosis. Dysregulation of lncRNAs has been associated with numerous types of human cancer. In the present study, the expression profile of differentially expressed genes (DEGs) and lncRNAs in gastric cancer (GC) samples and normal tissue samples was evaluated with bioinformatics. The biological functions of the predicted lncRNA TCONS_00068220 were focused on; the DEGs co-expressed with TCONS_00068220 were enriched in cancer-associated pathways. TCONS_00068220 was demonstrated to be upregulated in GC tissues and cell lines compared with normal controls. In addition, an increased rate of apoptosis was observed in NCI-N87 cells following transfection with small interfering RNA against TCONS_00068220. These data suggest that TCONS_00068220 may be associated with the pathogenesis of GC, and it may serve as a potential therapeutic target.

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Section: Introductionmentioning

confidence: 99%

Downregulated long non‑coding RNA TCONS_00068220 upregulates apoptosis in gastric cancer cells

et al. 2017

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“…Further evidence of the importance of this regulation comes from human HCC tissues where low PHB1 and CTCF levels and ICR binding activity of the proteins are associated with high levels of H19 and IGF2 genes. It is known that the H19-Igf2 axis is deregulated in HCC tissues and hepatoblastoma cell lines and during hepatocyte proliferation (14,15,19). To our knowledge, this is the first study providing mechanistic insight into the control of this axis in normal liver by the unique interaction of PHB1 with CTCF, a known modulator of the ICR region (23).…”

Section: Discussionmentioning

confidence: 82%

“…Both genes share enhancers and are asynchronously regulated at a site called the imprinting control region (ICR) 3 (13). Loss of imprinting of both Igf2 and H19 has been observed in hepatocellular carcinoma (HCC) tissues and cell lines (14,15). Igf2 is frequently activated in human cancers and in experimental liver carcinogenesis and is known to promote HCC growth (16,17).…”

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confidence: 99%

Prohibitin 1 Regulates the H19-Igf2 Axis and Proliferation in Hepatocytes

Ramani

Mavila

et al. 2016

Journal of Biological Chemistry

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Edited by Xiao-Fan WangProhibitin 1 (PHB1) is a mitochondrial chaperone that regulates cell growth. Phb1 knock-out mice exhibit liver injury and hepatocellular carcinoma (HCC). Phb1 knock-out livers show induction of tumor growth-associated genes, H19 and insulinlike growth factor 2 (Igf2). These genes are controlled by the imprinting control region (ICR) containing CCCTC-binding transcription factor (CTCF)-binding sites. Because Phb1 knockout mice exhibited induction of H19 and Igf2, we hypothesized that PHB1-mediated regulation of the H19-Igf2 axis might control cell proliferation in normal hepatocytes. H19 and Igf2 were induced (8 -20-fold) in 3-week-old Phb1 knock-out livers, in Phb1 siRNA-treated AML12 hepatocytes (2-fold), and HCC cell lines when compared with control. Phb1 knockdown lowered CTCF protein in AML12 by ϳ30% when compared with control. CTCF overexpression lowered basal H19 and Igf2 expression by 30% and suppressed Phb1 knockdown-mediated induction of these genes. CTCF and PHB1 co-immunoprecipitated and colocalized on the ICR element, and Phb1 knockdown lowered CTCF ICR binding activity. The results suggest that PHB1 and CTCF cooperation may control the H19-Igf2 axis. Human HCC tissues with high levels of H19 and IGF2 exhibited a 40 -50% reduction in PHB1 and CTCF expression and their ICR binding activity. Silencing Phb1 or overexpressing H19 in the mouse HCC cell line, SAMe-D, induced cell growth. Blocking H19 induction prevented Phb1 knockdown-mediated growth, whereas H19 overexpression had the reverse effect. Interestingly H19 silencing induced PHB1 expression. Taken together, our results demonstrate that the H19-Igf2 axis is negatively regulated by CTCF-PHB1 cooperation and that H19 is involved in modulating the growthsuppressive effect of PHB1 in the liver.

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“…It is an imprinted oncofetal gene, located on chromosome 11p15.5 and lies within 200 kb downstream of the IGF-2 gene. The loss of imprinting at the H19 locus typically results in an overexpression of H19 in liver cancer [67,68] . IGF-2 and H19 alleles are selectively expressed as these two genes are imprinted in the opposite directions [67] .…”

Section: H19mentioning

confidence: 99%

“…The loss of imprinting at the H19 locus typically results in an overexpression of H19 in liver cancer [67,68] . IGF-2 and H19 alleles are selectively expressed as these two genes are imprinted in the opposite directions [67] . The overexpression of an ectopic H19 gene enhances the tumorigenic properties of breast cancer cells according to previous investigations.…”

Section: H19mentioning

confidence: 99%

Non-coding RNAs: New therapeutic targets and opportunities for hepatocellular carcinoma

Ning

et al. 2016

Adv Mod Oncol Res

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Non-coding RNAs (ncRNA) are RNA molecules without protein coding functions owing to the lack of an open reading frame (ORF). Based on the length, ncRNAs can be divided into long and short ncRNAs; short ncRNAs include miRNAs and piRNAs. Hepatocellular carcinoma (HCC) is among the most frequent forms of cancer worldwide and its incidence is increasing rapidly. Studies have found that ncRNAs are likely to play a crucial role in a variety of biological processes including the pathogenesis and progression of HCC. In this review, we summarized the regulation mechanism and biological functions of ncRNAs in HCC with respect to its application in HCC diagnosis, therapy and prognosis.

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Biallelic expression of the H19 and IGF2 genes in hepatocellular carcinoma

Cited by 64 publications

References 22 publications

Downregulated long non‑coding RNA TCONS_00068220 upregulates apoptosis in gastric cancer cells

Downregulated long non‑coding RNA TCONS_00068220 upregulates apoptosis in gastric cancer cells

Prohibitin 1 Regulates the H19-Igf2 Axis and Proliferation in Hepatocytes

Non-coding RNAs: New therapeutic targets and opportunities for hepatocellular carcinoma

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