A functional screening identifies five micrornas controlling glypican‐3: role of mir‐1271 down‐regulation in hepatocellular carcinoma12. Issue 1 (7th January 2013)

• Record Type: Journal Article
• Authors: Maurel, Marion; Jalvy, Sandra; Ladeiro, Yannick; Combe, Chantal; Vachet, Laetitia; Sagliocco, Francis; Bioulac‐Sage, Paulette; Pitard, Vincent; Jacquemin‐Sablon, Hélène; Zucman‐Rossi, Jessica; Laloo, Benoît; Grosset, Christophe F.
• Is Part Of: Hepatology. Volume 57:Issue 1(2013:Jan.)
• Page Start: 195
• Page End: 204
• Publication Date: 2013-01-07
• Subjects: Heart -- Diseases -- Nursing -- Periodicals; Lungs -- Diseases -- Nursing -- Periodicals; Intensive care nursing -- Periodicals; Foie -- Maladies -- Périodiques; 616.362
• DOI: 10.1002/hep.25994
• Languages: English
• ISSNs: 0270-9139

Abstract

<abstract abstract-type="main" xml:lang="en"> <title>Abstract</title> <p>Hepatocellular carcinoma (HCC) is the major primary liver cancer. Glypican‐3 (<italic>GPC3</italic>), one of the most abnormally expressed genes in HCC, participates in liver carcinogenesis. Based on data showing that <italic>GPC3</italic> expression is posttranscriptionally altered in HCC cells compared to primary hepatocytes, we investigated the implication of microRNAs (miRNAs) in <italic>GPC3</italic> overexpression and HCC. To identify <italic>GPC3</italic>‐regulating miRNAs, we developed a dual‐fluorescence FunREG (functional, integrated, and quantitative method to measure posttranscriptional regulations) system that allowed us to screen a library of 876 individual miRNAs. Expression of candidate miRNAs and that of <italic>GPC3</italic> messenger RNA (mRNA) was measured in 21 nontumoral liver and 112 HCC samples. We then characterized the phenotypic consequences of modulating expression of one candidate miRNA in HuH7 cells and deciphered the molecular mechanism by which this miRNA controls the posttranscriptional regulation of <italic>GPC3</italic>. We identified five miRNAs targeting <italic>GPC3</italic> 3′‐untranslated region (UTR) and regulating its expression about the 876 tested. Whereas miR‐96 and its paralog miR‐1271 repressed <italic>GPC3</italic> expression, miR‐129‐1‐3p, miR‐1291, and miR‐1303 had an inducible effect. We report that miR‐1271 expression is down‐regulated in HCC tumor samples and inversely correlates with <italic>GPC3</italic> mRNA expression in a particular subgroup of HCC. We also report that miR‐1271 inhibits the growth of HCC cells in a <italic>GPC3</italic>‐dependent manner and induces cell death. <italic>Conclusion:</italic> Using a functional screen, we found that miR‐96, miR‐129‐1‐3p, miR‐1271, miR‐1291, and miR‐1303 differentially control <italic>GPC3</italic> expression in HCC cells. In a subgroup of HCC, the up‐regulation of <italic>GPC3</italic> was associated with a concomitant down‐regulation of its repressor miR‐1271. Therefore, we propose that <italic>GPC3</italic> overexpression and its associated oncogenic effects are linked to the down‐regulation of miR‐1271 in HCC. (H<sc>EPATOLOGY</sc> 2013)</p> </abstract>