title: MicroRNA-486-5p, which is downregulated in hepatocellular carcinoma, suppresses tumor growth by targeting PIK3R1.
abstract: Deregulated microRNAs and their roles in carcinogenesis and cancer progression have attracted much attention. In previous studies conducted in our laboratory, the Illumina Solexa massively parallel signature sequencing of miRNomes in nontumor and hepatocellular carcinoma (HCC) tissues revealed that miR-486-5p was significantly downregulated in HCC, but its role in HCC development remains unknown. In this study, miR-486-5p levels in HCC tissues and matched control tissues, and in seven HCC cell lines (QGY-7701, QGY-7703, QGY-7404, SMMC-7721, Huh7, HepG2, and PCL/PRF/5) and human normal liver cells (HL-7702), were tested by real-time quantitative RT-PCR. We found that the level of miR-486-5p was significantly decreased in HCC tissue and in all seven HCC cell lines. Overexpression of miR-486-5p markedly suppressed HCC cell proliferation, migration and invasion in vitro, and inhibited HCC growth in vivo. Mechanistically, miR-486-5p was confirmed to directly target PIK3R1 expression, thereby suppressing phosphatidylinositol 3-kinase-AKT pathway activation, by dual luciferase reporter assay and real-time quantitative RT-PCR and western blot analysis. In addition, PIK3R1 knockdown mimicked the effects of miR-486-5p overexpression by inhibiting HCC growth, migration, and invasion. Furthermore, correlation analysis, Kaplan-Meier estimates and Cox proportional hazard models showed an inverse correlation between miR-486-5p and PIK3R1, as well as a shorter time to recurrence after HCC resection, in patients with lower miR-486-5p expression. Hence, we conclude that miR-486-5p, which is frequently downregulated in HCC, inhibits HCC progression by targeting PIK3R1 and phosphatidylinositol 3-kinase-AKT activation.
authors.affiliation: Research department, Affiliated Tumor Hospital of Guangxi Medical University, Nanning, China.
authors.forename: Xin-Ping
authors.initials: XP
authors.lastname: Huang
authors.forename: Jin
authors.initials: J
authors.lastname: Hou
authors.forename: Xiao-Yun
authors.initials: XY
authors.lastname: Shen
authors.forename: Chao-Yuan
authors.initials: CY
authors.lastname: Huang
authors.forename: Xue-Hui
authors.initials: XH
authors.lastname: Zhang
authors.forename: Yu-An
authors.initials: YA
authors.lastname: Xie
authors.forename: Xiao-Ling
authors.initials: XL
authors.lastname: Luo
mesh_terms: D000818:Animals; D015153:Blotting, Western; D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics / Q000502:physiology; D049109:Cell Proliferation / Q000235:genetics / Q000502:physiology*; D058543:Class Ia Phosphatidylinositol 3-Kinase; D006801:Humans; D053208:Kaplan-Meier Estimate; D008113:Liver Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D058539:Phosphatidylinositol 3-Kinase / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics / Q000378:metabolism*; D014407:Tumor Cells, Cultured
chemical_list: D058543:Class Ia Phosphatidylinositol 3-Kinase; D035683:MicroRNAs; D058539:Phosphatidylinositol 3-Kinase; D019869:Phosphatidylinositol 3-Kinases; C560945:MIRN486 microRNA, human; C588001:PIK3R1 protein, human
keywords: hepatocellular carcinoma; metastasis; microRNA-486-5p; p85α; phosphatidylinositol 3-kinase