The H19 Non-Coding RNA Is Essential for Human Tumor Growth

By I. Matouk, N. Degroot, S. Mezan, S. Ayesh, R. Abu-lail, A. Hochberg, E. Galun. PLoS ONE, 2007

674 citations recorded by the source corpus.

Background Mutations and epigenetic aberrant signaling of growth factors pathways contribute to carcinogenesis. Recent studies reveal that non-coding RNAs are controllers of gene expression. H19 is an imprinted gene that demonstrates maternal monoallelic expression without a protein product; although its expression is shut off in most tissues postnatally, it is re-activated during adult tissue regeneration and tumorigenesis. Moreover, H19 is highly expressed in liver metastasis derived from a range of carcinomas. The objective of this study is to explore the role of H19 in carcinogenesis, and to determine its identification as an anti-tumor target. Methodology/ Principle Findings By controlling oxygen pressure during tumor cell growth and H19 expression levels, we investigated the role of H19 expression in vitro and in vivo in hepatocellular (HCC) and bladder carcinoma. Hypoxia upregulates the level of H19 RNA. Ablations of tumorigenicity of HCC and bladder carcinomas in vivo are seen by H19 knockdown which also significantly abrogates anchorage-independent growth after hypoxia recovery, while ectopic H19 expression enhances tumorigenic potential of carcinoma cells in vivo. Knocking-down H19 message in hypoxic stress severely diminishes p57kip2 induction. We identified a number of potential downstream targets of H19 RNA, including angiogenin and FGF18. Conclusions H19 RNA harbors pro-tumorigenic properties, thus the H19 gene behaves as an oncogene and may serve as a potential new target for anti-tumor therapy.

Subfields: Cancer Research, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/b883953743521bb86669f34ca798784f309bbe8d

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Citations in the corpus

The emergence of lncRNAs in cancer biology (2011, background): “In model systems, siRNA knockdown of H19 expression impaired cell growth and clonogenicity in lung cancer cell lines in vitro (35) and decreased xenograft tumor growth of Hep3B hepatocellular carcinoma cells in vivo (30).”
lncRNAdb: a reference database for long noncoding RNAs (2010, background): “These are described in the database and include putative or conﬁrmed cancer-associated lncRNAs, such as NDM29 (48), HOTAIR , which regulates metastatic progression (49), and H19, which has been described as both an oncogene (50) and a tumour suppressor (51).”
Roles, Functions, and Mechanisms of Long Non-coding RNAs in Cancer (2016, background): “H19 Highly expressed in hepatocellular carcinoma [153] 2 Genomics Proteomics Bioinformatics xxx (2016) xxx–xxx”
The Imprinted H19 LncRNA Antagonizes Let-7 MicroRNAs (2013, background): “, 2008) or an oncogene (Matouk et al., 2007) has been suggested.”
Long noncoding RNA in prostate, bladder, and kidney cancer. (2014, background): “5 Bladder Prognostic marker [83]; low-risk marker [85] Oncogene [4,45–47,50,51]; targeted therapy agent [91] Kidney Tumour suppressor [42]; tumour suppressor host [37] Prostate Putative susceptibility and diagnostic marker [43,44] HIF1A-AS1, AS2 14q23.”
microRNA-29 can regulate expression of the long non-coding RNA gene MEG3 in hepatocellular cancer (2011, background): “Long ncRNA that have been implicated as having a functional role in hepatocarcinogenesis or liver cancer growth include HULC, H19 and TUC338 (Matouk et al., 2007; Panzitt et al., 2007; Braconi et al., 2011).”
The Genetic Signatures of Noncoding RNAs (2009, background): “3 kb; imprinted (maternal allele active) at the Igf2 locus; strongly expressed during embryogenesis; up-regulated in various tumours Complex functions, influences growth by way of a cis control on Igf2 expression implicated as both a tumour suppressor and an oncogene siRNA knockdown; overexpression;”