title: MicroRNA-99a inhibits hepatocellular carcinoma growth and correlates with prognosis of patients with hepatocellular carcinoma.
abstract: In our in-depth analysis carried out by the Illumina Solexa massive parallel signature sequencing, microRNA-99a (miR-99a) was found to be the sixth abundant microRNA in the miRNome of normal human liver but was markedly down-regulated in hepatocellular carcinoma (HCC). Compelling evidence has suggested the important roles of microRNAs in HCC development. However, the biological function of miR-99a deregulation in HCC remains unknown. In this study, we found that miR-99a was remarkably decreased in HCC tissues and cell lines. Importantly, lower miR-99a expression in HCC tissues significantly correlated with shorter survival of HCC patients, and miR-99a was identified to be an independent predictor for the prognosis of HCC patients. Furthermore, restoration of miR-99a dramatically suppressed HCC cell growth in vitro by inducing the G(1) phase cell cycle arrest. Intratumoral injection of cholesterol-conjugated miR-99a mimics significantly inhibited tumor growth and reduced the α-fetoprotein level in HCC-bearing nude mice. Insulin-like growth factor 1 receptor (IGF-1R) and mammalian target of rapamycin (mTOR) were further characterized as the direct targets of miR-99a. Furthermore, protein levels of IGF-1R and mTOR were found to be inversely correlated with miR-99a expression in HCC tissues. miR-99a mimics inhibited IGF-1R and mTOR pathways and subsequently suppressed expression of cell cycle-related proteins, including cyclin D1 in HCC cells. Conclusively, miR-99a expression was frequently down-regulated in HCC tissues and correlates with the prognosis of HCC patients, thus proposing miR-99a as a prospective prognosis predictor of HCC. miR-99a suppresses HCC growth by inducing cell cycle arrest, suggesting miR-99a as potential tumor suppressor for HCC therapeutics.
authors: Institute of Immunology, Zhejiang University School of Medicine, Hangzhou 310058, China.
authors: Dong
authors: D
authors: Li
authors: Xingguang
authors: X
authors: Liu
authors: Li
authors: L
authors: Lin
authors: Jin
authors: J
authors: Hou
authors: Nan
authors: N
authors: Li
authors: Chunmei
authors: C
authors: Wang
authors: Pin
authors: P
authors: Wang
authors: Qian
authors: Q
authors: Zhang
authors: Peng
authors: P
authors: Zhang
authors: Weiping
authors: W
authors: Zhou
authors: Zhengxin
authors: Z
authors: Wang
authors: Guoshan
authors: G
authors: Ding
authors: Shi-Mei
authors: SM
authors: Zhuang
authors: Limin
authors: L
authors: Zheng
authors: Wenzhao
authors: W
authors: Tao
authors: Xuetao
authors: X
authors: Cao
mesh_terms: D000328:Adult; D000368:Aged; D006528:Carcinoma, Hepatocellular / Q000175:diagnosis / Q000235:genetics / Q000378:metabolism* / Q000628:therapy; D059447:Cell Cycle Checkpoints; D015536:Down-Regulation / Q000235:genetics; D005260:Female; D016193:G1 Phase; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008113:Liver Neoplasms / Q000175:diagnosis / Q000235:genetics / Q000378:metabolism* / Q000628:therapy; D008297:Male; D035683:MicroRNAs / Q000096:biosynthesis* / Q000235:genetics; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism; D011379:Prognosis; D012334:RNA, Neoplasm / Q000096:biosynthesis* / Q000235:genetics; D058570:TOR Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism; D000509:alpha-Fetoproteins / Q000235:genetics / Q000378:metabolism
chemical_list: C561679:MIRN99 microRNA, human; D035683:MicroRNAs; D009363:Neoplasm Proteins; D012334:RNA, Neoplasm; D000509:alpha-Fetoproteins; C546842:MTOR protein, human; D058570:TOR Serine-Threonine Kinases