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miR-206 regulates 5-FU resistance by targeting Bcl-2 in colon cancer cells

Authors Meng X, Fu R

Received 6 December 2017

Accepted for publication 7 February 2018

Published 29 March 2018 Volume 2018:11 Pages 1757—1765

DOI https://doi.org/10.2147/OTT.S159093

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Andrew Yee

Peer reviewer comments 2

Editor who approved publication: Dr Tohru Yamada


Xiaomin Meng, Rao Fu

Department of Applied Chemistry, Northeast Electric Power University, Jilin, People’s Republic of China

Introduction: Previous studies have found that miRNAs play a key role in drug resistance. Multiple reports show that miRNAs act as regulators in colorectal cancer (CRC) cells, but the role of miR-206 in CRC is still not well understood. The current study aimed to explore the potential function of miR-206 in 5-FU resistance.
Methods: To indentify the role of miR-206 in 5-FU resistance, the expression of miR-206 was examined by real-time polymerase chain reaction (RT-PCR) in 5-FU-resistant (FR) CRC (HCT116/FR and RKO/FR) and their parental cell lines. miR-206 mimic was transfected to 5-FU-FR CRC, and the 5-FU sensitivity was detected by MTS and flow cytometry. Using miRNA target prediction software, we found that miR-206 could target the 3' untranslated region (3'UTR) sequence of Bcl-2.
Results: miR-206 was found to be downregulated in 5-FU-FR CRC in comparison with their parental cell lines, suggesting its crucial relevance for colon cancer biology. Downregulation of miR-206 promoted drug resistance and decreased apoptosis of parental cells, while overexpression of miR-206 promoted drug cytotoxicity and apoptosis of HCT116/FR cells. We also identified miR-206 targeting Bcl-2 directly in CRC, which is required for miR-206 mediated-5-FU resistance.
Conclusion: Our results show that miR-206 targets Bcl-2 to mediate chemoresistance, proliferation, and apoptosis in CRC. This study provides a novel promising candidate for colon cancer therapy.

Keywords: miR-206, 5-FU, resistance, Bcl-2, colorectal cancer
 

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