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miR-206通过靶向结肠癌细胞中的Bcl-2来调节5-氟尿嘧啶耐药性。

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

作者信息

Meng Xiaomin, Fu Rao

机构信息

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

出版信息

Onco Targets Ther. 2018 Mar 29;11:1757-1765. doi: 10.2147/OTT.S159093. eCollection 2018.

DOI:10.2147/OTT.S159093
PMID:29636622
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5881530/
Abstract

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.

摘要

引言

先前的研究发现，微小RNA（miRNA）在耐药性中起关键作用。多项报告表明，miRNA在结直肠癌（CRC）细胞中充当调节因子，但miR-206在CRC中的作用仍未得到充分了解。当前的研究旨在探索miR-206在5-氟尿嘧啶（5-FU）耐药性中的潜在功能。

方法

为了确定miR-206在5-FU耐药性中的作用，通过实时聚合酶链反应（RT-PCR）检测了5-FU耐药（FR）CRC（HCT116/FR和RKO/FR）及其亲本细胞系中miR-206的表达。将miR-206模拟物转染至5-FU-FR CRC，并通过MTS和流式细胞术检测5-FU敏感性。使用miRNA靶标预测软件，我们发现miR-206可以靶向Bcl-2的3'非翻译区（3'UTR）序列。

结果

与亲本细胞系相比，发现miR-206在5-FU-FR CRC中表达下调，表明其与结肠癌生物学密切相关。miR-206的下调促进了亲本细胞的耐药性并降低了其凋亡，而miR-206的过表达促进了HCT116/FR细胞的药物细胞毒性和凋亡。我们还确定了miR-206在CRC中直接靶向Bcl-2，这是miR-206介导的5-FU耐药性所必需的。

结论

我们的结果表明，miR-206靶向Bcl-2以介导CRC中的化疗耐药性、增殖和凋亡。本研究为结肠癌治疗提供了一种新的有前景的候选药物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e8f7/5881530/8b8c24770235/ott-11-1757Fig6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e8f7/5881530/31f0d68feb2b/ott-11-1757Fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e8f7/5881530/1971a283880f/ott-11-1757Fig2.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e8f7/5881530/379a5a5350d6/ott-11-1757Fig5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e8f7/5881530/8b8c24770235/ott-11-1757Fig6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e8f7/5881530/31f0d68feb2b/ott-11-1757Fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e8f7/5881530/1971a283880f/ott-11-1757Fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e8f7/5881530/3d2adbac4264/ott-11-1757Fig3.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e8f7/5881530/379a5a5350d6/ott-11-1757Fig5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e8f7/5881530/8b8c24770235/ott-11-1757Fig6.jpg

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