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Epigenetics mechanisms mediate the miR-125a/BRMS1 axis to regulate invasion and metastasis in gastric cancer

Authors Xiong J, Tu Y, Feng Z, Li D, Yang Z, Huang Q, Li Z, Cao Y, Jie Z

Received 28 March 2019

Accepted for publication 17 August 2019

Published 12 September 2019 Volume 2019:12 Pages 7513—7525

DOI https://doi.org/10.2147/OTT.S210376

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Ms Aruna Narula

Peer reviewer comments 2

Editor who approved publication: Dr Carlos E Vigil


Jianbo Xiong,1,* Yi Tu,2,* Zongfeng Feng,1,* Daojiang Li,3 Zhouwen Yang,1 Qiuxia Huang,4 Zhengrong Li,1 Yi Cao,1 Zhigang Jie1

1Department of Gastrointestinal Surgery, First Affiliated Hospital, Nanchang University, Nanchang 330006, Jiangxi Province, People’s Republic of China; 2Department of Pathology, First Affiliated Hospital, Nanchang University, Nanchang 330006, Jiangxi Province, People’s Republic of China; 3Department of General Surgery, Zhongnan Hospital of Wuhan University, Wuhan 430071, Hubei Province, People’s Republic of China; 4Department of Nursing, First Affiliated Hospital, Nanchang University, Nanchang 330006, Jiangxi Province, People’s Republic of China

*These authors contributed equally to this work

Correspondence: Zhigang Jie; Yi Cao
Department of Gastrointestinal Surgery, First Affiliated Hospital, Nanchang University, No.17 Yongwai Zheng Road, Nanchang 330006, Jiangxi Province, People’s Republic of China
Tel +86 7 918 869 2522
Email Jiezg123@126.com; doctorcaoyi@126.com

Purpose: Altered expression of breast cancer metastasis suppressor 1 (BRMS1), is a tumor suppressor, which is found in many types of cancers, including gastric cancer (GC), but the mechanism by which BRMS1 inhibits invasion and metastasis in GC is unknown. The aim of the study was to investigate the molecular mechanisms of miR-125a/BRMS1 in GC.
Materials and methods: The expression of BRMS1 and miR-125a were detected by quantitative real-time PCR (qRT-PCR) and analyzed by bioinformatics. BSP and MSP were used to detecte the methylation status of miR-125a and BRMS1 which was treated by 5-Aza or not. Western Blot and qRT-PCR were used to analyze the expression of BRMS1 and EZH2. Transwell was performed to explore the invasion and metastasis ability of GC cells. The nude mice were used for the tumor formation assay.
Results: BRMS1 may be regulated by copy number variation (CNV), methylation and miR-125a-5p. As one of the essential components of PRC2, EZH2 is an important regulatory factor resulting in the low expression of miR-125a. An epigenetic mechanism mediates the miR-125a/BRMS1 axis to inhibit the invasion and metastasis of GC cells. In vivo experiments, it is also showed that BRMS1 is involved in invasion and metastasis but not the proliferation in GC.
Conclusion: These studies shed light on the mechanism of BRMS1 inhibition of GC invasion and metastasis and the development of new drugs targeting the miR-125a/BRMS1 axis, which will be a promising therapeutic strategy for GC and other human cancers.

Keywords: gastric cancer, miR-125a/BRMS1 axis, epigenetic, EZH2, invasion and metastasis
 

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