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

Lin Zhou; Xin Liang; Lingling Zhang; Liyan Yang; Norio Nagao; Hongkun Wu; Chang Liu; Shengchao Lin; Guoxiang Cai; Jianwen Liu

doi:10.18632/oncotarget.10460

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Research Papers:

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

Lin Zhou _, Xin Liang, Lingling Zhang, Liyan Yang, Norio Nagao, Hongkun Wu, Chang Liu, Shengchao Lin, Guoxiang Cai and Jianwen Liu

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Oncotarget. 2016; 7:51943-51954. https://doi.org/10.18632/oncotarget.10460

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Abstract

Lin Zhou1,*, Xin Liang2,*, Lingling Zhang2, Liyan Yang2, Norio Nagao3, Hongkun Wu1, Chang Liu1, Shengchao Lin2, Guoxiang Cai4, Jianwen Liu2

1Department of Laboratory Medicine, Changzhen Hospital, Second Military Medical University, Shanghai 200003, China

2State 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

3Department of Life and Environmental Sciences, Prefectural University of Hiroshima, Shobara, 727-0023 Japan

4Department 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: [email protected]

Guoxiang Cai, email: [email protected]

Jianwen Liu, email: [email protected]

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.

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Research Papers:

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

Abstract