TAILIEUCHUNG - Báo cáo khoa học: MicroRNA-373, a new regulator of protein phosphatase 6, functions as an oncogene in hepatocellular carcinoma

MicroRNAs are a class of small noncoding RNAs that function as key reg-ulators of gene expression at the post-transcriptional level. Recently, micr-oRNA-373 (miR-373) has been found to function as an oncogene in testicular germ cell tumors. | IFEBS Journal MicroRNA-373 a new regulator of protein phosphatase 6 functions as an oncogene in hepatocellular carcinoma Nannan Wu Xuyuan Liu Xuemei Xu Xingxing Fan Min Liu Xin Li Qiping Zhong and Hua Tang Tianjin Life Science Research Center and Basic Medical School Tianjin MedicalUniversity China Keywords cell cycle hepatocellular carcinoma miRNA miRNA-373 protein phosphatase 6 catalytic subunit PPP6C Correspondence H. Tang Tianjin Life Science Research Center and Basic Medical School Tianjin MedicalUniversity Tianjin 300070 China Fax 86 22 23542503 Tel 86 22 23542503 E-mail htang2002@ These authors contributed equally to this work Received 9 January 2011 revised 17 March 2011 accepted 5 April 2011 doi MicroRNAs are a class of small noncoding RNAs that function as key regulators of gene expression at the post-transcriptional level. Recently micr-oRNA-373 miR-373 has been found to function as an oncogene in testicular germ cell tumors. In our study we found that miR-373 is upregu-lated in human hepatocellular carcinoma HCC tissues as compared with adjacent normal tissues and promotes the proliferation of the HCC cell lines HepG2 and QGY-7703 by regulating the transition between G1-phase-and S-phase. The gene encoding the protein phosphatase 6 catalytic subunit PPP6C a negative cell cycle regulator was identified as a direct target gene of miR-373 by use of a fluorescent reporter assay. The mRNA and protein levels of PPP6C were both inversely correlated with the miR-373 expression level. Overexpression of PPP6C abolished the regulation of cell cycle and cell growth exercised by miR-373 in HepG2 cells. These results indicate that miR-373 plays an important role in the pathogenesis of HCC and may be a new biomarker in HCC. Our results demonstrate that miR-373 can regulate cell cycle progression by targeting PPP6C transcripts and promotes the growth activity of HCC cells in vitro. The downregulation of PPP6C by miR-373 may .

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