Characterization of HULC, a novel gene with striking up-regulation in hepatocellular carcinoma, as noncoding RNA.

By K. Panzitt, M. M. Tschernatsch, C. Guelly, T. Moustafa, Martin Stradner, H. Strohmaier, Charles R. Buck, H. Denk, R. Schroeder, M. Trauner and 1 more. Gastroenterology, 2007

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BACKGROUND & AIMS Recent studies have highlighted the role of noncoding RNAs (ncRNAs) in carcinogenesis, and suggested that this class of genes might be used as biomarkers in cancer. We searched the human genome for novel genes including ncRNAs related to hepatocellular carcinoma (HCC). METHODS An HCC-specific gene library was generated and screened for deregulated genes with 46 HCCs, 4 focal nodular hyperplasias, and 7 cirrhoses utilizing cDNA arrays. Sequencing of library clones identified a novel ncRNA as the most up-regulated gene in HCC. This gene was also cloned from different monkeys and characterized by quantitative RT-PCR, Northern blot analysis and in situ hybridization. Structural and functional studies included comparative sequence and protein expression analyses, quantitative RT-PCR of polysomal preparations, and siRNA-mediated knockdown experiments. RESULTS The most up-regulated gene in HCC named highly up-regulated in liver cancer (HULC) was characterized as a novel mRNA-like ncRNA. HULC RNA is spliced and polyadenlyated, and resembles the mammalian LTR transposon 1A. It does not contain substantial open reading frames, and no native translation product was detected. HULC is present in the cytoplasm, where it copurifies with ribosomes. siRNA-mediated knockdown of HULC RNA in 2 HCC cell lines altered the expression of several genes, 5 of which were known to be affected in HCC, suggesting a role for HULC in post-transcriptional modulation of gene expression. CONCLUSIONS HULC is the first ncRNA with highly specific up-regulation in HCC. Because HULC was detected in blood of HCC patients, a potential use as novel biomarker can be envisaged.

Subfields: Cancer Research, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/b07804c7e95813972896de3d7e55a415d4a49321

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Citations in the corpus

Long Non-coding RNAs in the Cytoplasm (2016, background): “It is present in the cytoplasm, spliced, polyadenylated, and resembles the mammalian LTR transposon 1A [60].”
LNCipedia: a database for annotated human lncRNA transcript sequences and structures (2012, background): “Notable examples are XIST (X inactive-specific transcript) (6), HOTAIR (HOX transcript antisense RNA) (7) and HULC (highly up-regulated in liver cancer) (8).”
Transposable Elements Are Major Contributors to the Origin, Diversification, and Regulation of Vertebrate Long Noncoding RNAs (2013, background): “The presence of exonized TEs has been reported for some of these lncRNAs, such as XIST [46], UCA1 [75], HULC [76], PCAT14 [77] and SLC7A2-IT1A/B [78].”
Long Non-Coding RNA in the Pathogenesis of Cancers (2019, background): “3, which is firstly characterized as a novel mRNA-like lncRNA, and HULC is shown to be significantly upregulated in human HCC [224].”
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).”
A ceRNA hypothesis: the Rosetta stone of a hidden RNA language? (2011, background): “It was reported that the lncRNA HULC is one of themost upregulated of all genes in hepatocellular carcinoma (Panzitt et al., 2007).”