title: microRNA-29a suppresses cell proliferation by targeting SPARC in hepatocellular             carcinoma.
abstract: In the present study, we constructed a lentivirus vector encoding the miR-29a             precursor and established two stably infected cell lines, PLC-29a and 97L-29a.             The overexpression of miR-29a was confirmed by TaqMan RT-PCR and significantly             suppressed the growth of the hepatocellular carcinoma cell lines MHCC-97L and             PLC. Dual-luciferase reporter assays indicated that the SPARC mRNA 3'UTR was directly             targeted by miR-29a since the mutated 3'UTR was not affected. Silencing SPARC             expression by RNAi knockdown resulted in a similar effect as miR-29a overexpression             on hepatocellular carcinoma (HCC) cell growth regulation. Anti-miR-29a oligonucleotides             (AMOs) upregulated the levels of SPARC in the HCC cells. The phosphorylation of             AKT/mTOR downstream of SPARC was inhibited in miR-29a-overexpressing HCC cells.             We further examined and compared the expression levels of miR-29a in HCC tissues             and the corresponding nearby non-cancerous liver tissues of 110 patients with             HCC by qRT-PCR, and significantly lower expression of miR-29a was observed in             the tissues affected by HCC. Our findings demonstrate that the expression of miR-29a             is important in the regulation of the SPARC-AKT pathway and HCC growth.
authors.affiliation: Department of Biochemistry and Molecular Biology, Shanghai Medical                     College, Fudan University, Key Laboratory of Glycoconjugate Research,                     Ministry of Public Health, Shanghai 200032, P.R. China.
authors.forename: Xu-Chao
authors.initials: XC
authors.lastname: Zhu
authors.forename: Qiong-Zhu
authors.initials: QZ
authors.lastname: Dong
authors.forename: Xiao-Fei
authors.initials: XF
authors.lastname: Zhang
authors.forename: Biao
authors.initials: B
authors.lastname: Deng
authors.forename: Hu-Liang
authors.initials: HL
authors.lastname: Jia
authors.forename: Qin-Hai
authors.initials: QH
authors.lastname: Ye
authors.forename: Lun-Xiu
authors.initials: LX
authors.lastname: Qin
authors.forename: Xing-Zhong
authors.initials: XZ
authors.lastname: Wu
mesh_terms: D000328:Adult; D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D055785:Gene Knockdown Techniques; D006801:Humans; D008099:Liver / Q000378:metabolism; D008113:Liver Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D008297:Male; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D008875:Middle Aged; D015676:Osteonectin; D010766:Phosphorylation; D011499:Protein Processing, Post-Translational; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D034622:RNA Interference; D015398:Signal Transduction; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism; D025521:Tumor Suppressor Proteins / Q000235:genetics* / Q000378:metabolism; D015854:Up-Regulation
chemical_list: C532045:MIRN29a microRNA, human; D035683:MicroRNAs; D015676:Osteonectin; C577241:SPARC protein, human; D025521:Tumor Suppressor Proteins; C546842:MTOR protein, human; D051057:Proto-Oncogene Proteins c-akt; D058570:TOR Serine-Threonine Kinases