Mol. Cells 2018; 41(6): 523~531  https://doi.org/10.14348/molcells.2018.2200
MicroRNA-3200-5p Promotes Osteosarcoma Cell Invasion via Suppression of BRMS1
Gen Li1,3, Li Li2,3, Qi Sun1, Jiezhou Wu1, Wei Ge1, Guanghua Lu1, and Ming Cai1,*
1Department of Orthopedics, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai 200072, China, 2Department of Orthopedics, Changhai Hospital of Shanghai, The Second Military Medical University, Shanghai 200433, China, 3These authors contributed equally to this work.
*Correspondence: cmdoctor@tongji.edu.cn; cmdoctor@yeah.net
Received September 4, 2017; Revised January 31, 2018; Accepted February 18, 2018.; Published online June 11, 2018.
© Korean Society for Molecular and Cellular Biology. All rights reserved.

This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 3.0 Unported License. To view a copy of this license, visit (http://creativecommons.org/licenses/by-nc-sa/3.0/).
ABSTRACT
Tumour metastasis is one of the most serious challenges of cancer as it is the major cause of mortality in patients with solid tumours, including osteosarcoma (OS). In this regard, anti-metastatic genes have potential for metastasis inhibition strategies. Recent evidence showed the importance of breast cancer metastasis suppressor 1 (BRMS1) in control of OS invasiveness, but the regulation of BRMS1 in OS remains largely unknown. Here, we used bioinformatics analyses to predict BRMS1-targeting microRNAs (miRNAs), and the functional binding of miRNAs to BRMS1 mRNA was evaluated using a dual luciferase reporter assay. Among all BRMS1-targeting miRNAs, only miR-151b, miR-7-5p and miR-3200-5p showed significant expression in OS specimens. Specifically, we found that only miR-3200-5p significantly inhibited protein translation of BRMS1 via pairing to the 3'-UTR of the BRMS1 mRNA. Moreover, we detected significantly lower BRMS1 and significantly higher miR-3200-5p in the OS specimens compared to the paired adjacent non-tumour bone tissues. Furthermore, BRMS1 and miR-3200-5p levels were inversely correlated to each other. Low BRMS1 was correlated with metastasis and poor patient survival. In vitro, overexpression of miR-3200-5p significantly decreased BRMS1 levels and promoted OS cell invasion and migration, while depletion of miR-3200-5p significantly increased BRMS1 levels and inhibited OS cell invasion and migration. Thus, our study revealed that miR-3200-5p may be a critical regulator of OS cell invasiveness.
Keywords: breast cancer metastasis suppressor 1 (BRMS1), miR-3200-5p, osteosarcoma (OS)


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30 June 2018 Volume 41,
Number 6, pp. 495~611

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