title: MicroRNA-3127 promotes cell proliferation and tumorigenicity in hepatocellular carcinoma by disrupting of PI3K/AKT negative regulation.
abstract: Recent studies have shown that multiple phosphatases deactivate the PI3K/AKT signaling pathway. Here we demonstrated that, by suppressing multiple phosphatases, miR-3127 promotes growth of hepatocellular carcinoma (HCC). Our study also reveals clinical significance of miR-3127 expression in HCC patients. MiR-3127 expression was markedly upregulated in HCC tissues and cells. Furthermore, high miR-3127 expression was associated with an aggressive phenotype and poor prognosis. MiR-3127 overexpression promoted HCC cell proliferation in vitro and tumor growth in vivo. Also, miR-3127 accelerated G1-S transition by activating AKT/ FOXO1 signaling, by directly targeting the 3' untranslated regions (3`UTR) of pleckstrin homology domain leucine-rich repeat protein phosphatase 1/2 (PHLPP1/2), inositol polyphosphate phosphatase 4A (INPP4A), and inositol polyphosphate-5-phosphatase J (INPP5J) mRNA, repressing their expression. In agreement, the miRNA antagonist antagomir-3127 suppressed HCC cell proliferation and tumor growth by inhibiting the AKT/FOXO1 signaling. Taken together, these findings suggest that silencing miR-3127 might be a potential therapeutic strategy.
authors: Department of Hepatobiliary Surgery, Affiliated Hospital of Guiyang Medical College, Guiyang, China.
authors: Jianxin
authors: J
authors: Jiang
authors: Zhongnan Hospital of Wuhan University, Institute of Hepatobiliary Diseases of Wuhan University, Transplant Center of Wuhan University, Hubei Key Laboratory of Medical Technology on Transplantation, Wuhan, China.
authors: Yi
authors: Y
authors: Zhang
authors: Department of Hepatobiliary Surgery, Affiliated Hospital of Guiyang Medical College, Guiyang, China.
authors: Yuting
authors: Y
authors: Guo
authors: Department of Hepatobiliary Surgery, Affiliated Hospital of Guiyang Medical College, Guiyang, China.
authors: Chao
authors: C
authors: Yu
authors: Department of Hepatobiliary Surgery, Affiliated Hospital of Guiyang Medical College, Guiyang, China.
authors: Meiyuan
authors: M
authors: Chen
authors: Department of Hepatobiliary Surgery, Affiliated Hospital of Guiyang Medical College, Guiyang, China.
authors: Zhu
authors: Z
authors: Li
authors: Department of Hepatobiliary Surgery, Affiliated Hospital of Guiyang Medical College, Guiyang, China.
authors: Se
authors: S
authors: Tian
authors: Department of Hepatobiliary Surgery, Affiliated Hospital of Guiyang Medical College, Guiyang, China.
authors: Chengyi
authors: C
authors: Sun
mesh_terms: D000818:Animals; D063646:Carcinogenesis; D006528:Carcinoma, Hepatocellular / Q000201:enzymology / Q000235:genetics / Q000473:pathology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000502:physiology; D056945:Hep G2 Cells; D064593:Heterografts; D006801:Humans; D008113:Liver Neoplasms / Q000201:enzymology / Q000235:genetics / Q000473:pathology*; D051379:Mice; D008807:Mice, Inbred BALB C; D035683:MicroRNAs / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D015398:Signal Transduction; D014162:Transfection; D015854:Up-Regulation
chemical_list: C000605234:MIRN3127 microRNA, human; D035683:MicroRNAs; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt
keywords: INPP4A; PHLPP; PI3K/AKT pathway; hepatocellular carcinoma; miR-3127