title: Mir-765 promotes cell proliferation by downregulating INPP4B expression in human hepatocellular carcinoma.
abstract: microRNAs (miRNAs) dysregulation is widely involved in cancer progression and contributed to sustained cell proliferation by directly targeting multiple targets. Therefore, better understanding the underlying mechanism of miRNA in carcinogenesis may improve diagnostic and therapeutic strategies for malignancy. In our study, we found that mir-765 is upregulated in both hepatocellular carcinoma (HCC) cell lines and tissues, compared to human normal liver cell line and adjacent non-cancerous tissues, respectively. Overexpression of mir-765 increased HCC cells proliferation and tumorigenicity, whereas inhibition of mir-765 reverses this effect. Furthermore, we demonstrated that INPP4B as a direct target of mir-765 and ectopic expression of mir-765 repressed INPP4B expression, resulting in upregulation of p-AKT, Cyclin D1, and downregulation of p-FOXO3a, p21 expression in HCC. Strikingly, we found that silencing the expression of INPP4B is the essential biological function of miR-765 during HCC cell proliferation. Collectively, our findings reveal that miR-765 is a potential onco-miR that participates in carcinogenesis of human HCC by suppressing INPP4B expression, and might represent a potential therapeutic target for HCC patients.
authors.affiliation: Department of General Surgery, the First Affiliated Hospital of Gannan Medical University, Guangzhou, Guangdong, China.
authors.forename: Bin-Hui
authors.initials: BH
authors.lastname: Xie
authors.affiliation: Department of General Surgery, the First Affiliated Hospital of Gannan Medical University, Guangzhou, Guangdong, China.
authors.forename: Xiao
authors.initials: X
authors.lastname: He
authors.affiliation: Department of Oncology, the First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong, China.
authors.forename: Rui-Xi
authors.initials: RX
authors.lastname: Hua
authors.affiliation: Department of Nuclear Medicine, the First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong, China.
authors.forename: Bing
authors.initials: B
authors.lastname: Zhang
authors.affiliation: Department of Interventional Radiology, the First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong, China.
authors.forename: Guo-Sheng
authors.initials: GS
authors.lastname: Tan
authors.affiliation: Department of Biochemistry, University of Leicester, Leicester, UK.
authors.forename: Shi-Qiu
authors.initials: SQ
authors.lastname: Xiong
authors.affiliation: Department of Interventional Radiology, the First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong, China.
authors.forename: Liang-Shuai
authors.initials: LS
authors.lastname: Liu
authors.affiliation: Department of Interventional Radiology, the First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Chen
authors.affiliation: Department of Interventional Radiology, the First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong, China.
authors.forename: Jian-Yong
authors.initials: JY
authors.lastname: Yang
authors.affiliation: Department of General Surgery, the First Affiliated Hospital of Gannan Medical University, Guangzhou, Guangdong, China.
authors.forename: Xiao-Nong
authors.initials: XN
authors.lastname: Wang
authors.affiliation: Department of Oncology, the First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong, China.|Department of Interventional Radiology, the First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong, China.
authors.forename: He-Ping
authors.initials: HP
authors.lastname: Li
mesh_terms: D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000235:genetics*; D002471:Cell Transformation, Neoplastic / Q000235:genetics*; D019938:Cyclin D1 / Q000096:biosynthesis; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000096:biosynthesis; D015536:Down-Regulation; D000071316:Forkhead Box Protein O3 / Q000096:biosynthesis; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics* / Q000473:pathology; D035683:MicroRNAs / Q000096:biosynthesis / Q000235:genetics*; D010744:Phosphoric Monoester Hydrolases / Q000096:biosynthesis* / Q000235:genetics; D051057:Proto-Oncogene Proteins c-akt / Q000096:biosynthesis
chemical_list: C530104:CCND1 protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; C499517:FOXO3 protein, human; D000071316:Forkhead Box Protein O3; C000600151:MIRN765 microRNA, human; D035683:MicroRNAs; D019938:Cyclin D1; D051057:Proto-Oncogene Proteins c-akt; D010744:Phosphoric Monoester Hydrolases; C053153:phosphatidylinositol-3,4-bisphosphate 4-phosphatase
keywords: INPP4B; human hepatocellular carcinoma; miR-765; proliferation