MiR-27a-3p functions as an oncogene in gastric cancer by targeting BTG2

Abstract

// Lin Zhou 1, * , Xin Liang 2, * , Lingling Zhang 2 , Liyan Yang 2 , Norio Nagao 3 , Hongkun Wu 1 , Chang Liu 1 , Shengchao Lin 2 , Guoxiang Cai 4 , Jianwen Liu 2 1 Department of Laboratory Medicine, Changzhen Hospital, Second Military Medical University, Shanghai 200003, China 2 State Key Laboratory of Bioreactor Engineering & Shanghai Key Laboratory of New Drug Design, School of Pharmacy, East China University of Science and Technology, Shanghai, 200237, China 3 Department of Life and Environmental Sciences, Prefectural University of Hiroshima, Shobara, 727-0023 Japan 4 Department of Colorectal Surgery, Fudan University Shanghai Cancer Center, Shanghai 200032,China * Authorship note: Lin Zhou and Xin Liang contributed equally to this work as co-first authors Correspondence to: Lin Zhou, email: lynnzhou36@163.com Guoxiang Cai, email: gxcai@fudan.edu.cn Jianwen Liu, email: liujian@ecust.edu.cn Keywords: miR-27a-3p, apoptosis, BTG2, gastric cancer, cell proliferation Abbreviations: miRNA, microRNA; GC, Gastric cancer; BTG2, B-cell translocation gene2; UTR, untranslated region Received: October 22, 2015     Accepted: June 17, 2016     Published: July 07, 2016 ABSTRACT microRNA-27a (miR-27a) is frequently dysregulated in human carcinoma, including gastric cancer. The B-cell translocation gene 2 (BTG2) has been implicated in gastric carcinogenesis. However, till now, the link between miR-27a and BTG2 in gastric cancer has not been reported. Here, we found that two isoforms of mature miR-27a, miR-27a-5p and miR-27-3p, were both frequently overexpressed in gastric cancer tissues and cell lines, whereas the expression level of miR-27-3p in gastric cancer was significantly higher than that of miR-27a-5p. And overexpression of miR-27a-3p, but not miR-27a-5p, markedly promoted gastric cancer cell proliferation in vitro as well as tumor growth in vivo. Further experiments revealed that BTG2 was a direct and functional target of miR-27a-3p in gastric cancer and miR-27a-3p inhibition obviously up-regulated the expression of BTG2. In turn, overexpression of BTG2 triggered G1/S cell cycle arrest, induced subsequent apoptosis, and inhibited C-myc activation following Ras/MEK/ERK signaling pathway, which involved in the biological effects of miR-27a-3p/BTG2 axis on gastric carcinogenesis and cancer progression. Overall, these results suggested that the miR-27a-3p/BTG2 axis might represent a promising diagnostic biomarker for gastric cancer patients and could be a potential therapeutic target in the management of gastric cancer.