Mir-765 promotes cell proliferation by downregulating INPP4B expression in human hepatocellular carcinoma

Article type: Research Article

Authors: Xie, Bin-Hui^a | He, Xiao^a | Hua, Rui-Xi^b | Zhang, Bing^c | Tan, Guo-Sheng^d | Xiong, Shi-Qiu^e | Liu, Liang-Shuai^d | Chen, Wei^d | Yang, Jian-Yong^d | Wang, Xiao-Nong^{a; *} | Li, He-Ping^{b; d; *}

Affiliations: [a] Department of General Surgery, the First Affiliated Hospital of Gannan Medical University, Guangzhou, Guangdong, China | [b] Department of Oncology, the First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong, China | [c] Department of Nuclear Medicine, the First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong, China | [d] Department of Interventional Radiology, the First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong, China | [e] Department of Biochemistry, University of Leicester, Leicester, UK

Correspondence: [*] Corresponding authors: He-Ping Li, Department of Oncology, the First Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510080, China; Department of Interventional Radiology, the First Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510080, Guangdong, China. Tel./Fax: +86 20 37621096; E-mail: drlihp@126.com; Xiao-Nong Wang, Department of General Surgery, the First Affiliated Hospital of Gannan Medical University, Ganzhou 341000, Guangdong, China. Tel./Fax: +86 0797 8266000; E-mail: riverstr@163.com

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.

Keywords: miR-765, INPP4B, proliferation, human hepatocellular carcinoma

DOI: 10.3233/CBM-160579

Journal: Cancer Biomarkers, vol. 16, no. 3, pp. 405-413, 2016