MicroRNA-602 regulating tumor suppressive gene RASSF1A is overexpressed in hepatitis B virus-infected liver and hepatocellular carcinoma.
OBJECTIVE
It is important to understand the role of microRNA in the transformation from chronic HBV hepatitis to hepatocellular carcinoma in hepatocarcinogenesis. Relationship of microRNA-602 with chronic HBV hepatitis, liver cirrhosis and HCC was investigated in this article.


RESULTS
(1) 14 MicroRNAs were aberrantly expressed in HCC and CL compared with NL. Among these, microRNA-602 expression in CH, LC, NT and HCC was 2.939, 3.234, 2.439 and 4.134 times of that in NL respectively, which was significantly different (p < 0.01 for all vs. NL); RASSF1A expression in LC and HCC was lower than that in NL, while P73 protein expression in CL was higher than that in NL and HCC. (2) MicroRNA-602 expression in HepG2 2.2.15 and HepG2-HBX was 2.643 and 3.48 times of that in HepG2 (p < 0.05 for both). (3) MicroRNA-602 inhibition in HepG2 cells was associated with RASSF1A mRNA and protein expression increased to 4.37, 3.01 times respectively of those not, with cell apoptosis increased and cell proliferation rate decreased significantly, changes were similar in HepG2-HBX cells.


METHODS
(1) MicroRNA expression was investigated in normal (NL), chronic HBV hepatitis (CH), HBV-positive cirrhotic (CL), HBV-positive HCC and corresponding normal para-tumorous livers (NT) and hepatoma cells was evaluated with microRNA microarray and verified by real-time PCR, and microRNA-602 was selected for further study. Expression of miR602-target genes RASSF1A and P73 were detected with RT-PCR and western blot. (2) MicroRNA-602 expression in HepG2 and HepG2-HBX was inhibited by miR-602 inhibitor transfection; RASSF1A and P73 expression was detected and cell apoptosis and proliferation were detected.


CONCLUSIONS
MicroRNA-602 plays a pro-carcinogenic role in HBV-related hepatocarcinogenesis by inhibiting RASSF1A. MicroRNA-602 might be an early diagnostic marker for HBV-mediated HCC.
Yang
Lian
L
Hepatobiliary Surgery Center, Union Hospital, HUST, Wuhan, China.
Ma
Zhaolong
Z
Wang
Dongdong
D
Zhao
Wenyue
W
Chen
Libo
L
Wang
Guobin
G
D006528:Carcinoma, Hepatocellular / Q000150:complications / Q000503:physiopathology; D045744:Cell Line, Tumor; D004268:DNA-Binding Proteins / Q000235:genetics; D015870:Gene Expression; D020869:Gene Expression Profiling; D056945:Hep G2 Cells; D019694:Hepatitis B, Chronic / Q000150:complications / Q000378:metabolism; D006801:Humans; D008103:Liver Cirrhosis / Q000150:complications / Q000235:genetics; D008113:Liver Neoplasms / Q000150:complications / Q000503:physiopathology; D035683:MicroRNAs / Q000378:metabolism*; D009687:Nuclear Proteins / Q000235:genetics; D000072160:Tumor Protein p73; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism
D004268:DNA-Binding Proteins; C559285:MIRN602 microRNA, human; D035683:MicroRNAs; D009687:Nuclear Proteins; C411762:RASSF1 protein, human; C000606460:TP73 protein, human; D000072160:Tumor Protein p73; D025521:Tumor Suppressor Proteins