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微小RNA-27a-3p通过靶向BTG2在胃癌中发挥癌基因作用。

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

作者信息

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

机构信息

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

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.

出版信息

Oncotarget. 2016 Aug 9;7(32):51943-51954. doi: 10.18632/oncotarget.10460.

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.

摘要

微小RNA-27a(miR-27a)在包括胃癌在内的人类癌症中经常发生失调。B细胞易位基因2(BTG2)与胃癌发生有关。然而,迄今为止,miR-27a与BTG2在胃癌中的联系尚未见报道。在此,我们发现成熟miR-27a的两种异构体,即miR-27a-5p和miR-27-3p,在胃癌组织和细胞系中均经常过度表达,而miR-27-3p在胃癌中的表达水平显著高于miR-27a-5p。并且,miR-27a-3p而非miR-27a-5p的过表达显著促进了体外胃癌细胞增殖以及体内肿瘤生长。进一步实验表明,BTG2是胃癌中miR-27a-3p的直接功能性靶标,抑制miR-27a-3p明显上调了BTG2的表达。反过来,BTG2的过表达引发G1/S期细胞周期阻滞,诱导随后的细胞凋亡,并抑制Ras/MEK/ERK信号通路下游的C-myc激活,这涉及miR-27a-3p/BTG2轴对胃癌发生和癌症进展的生物学效应。总体而言,这些结果表明,miR-27a-3p/BTG2轴可能是胃癌患者有前景的诊断生物标志物,并且可能是胃癌治疗的潜在靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dd78/5239526/a6c1c12c137f/oncotarget-07-51943-g001.jpg

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