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

被引:57
|
作者
Meng, Xiaomin [1 ]
Fu, Rao [1 ]
机构
[1] Northeast Elect Power Univ, Dept Appl Chem, 169 Changchun St, Jilin 132012, Jilin, Peoples R China
来源
ONCOTARGETS AND THERAPY | 2018年 / 11卷
关键词
miR-206; 5-FU; resistance; Bcl-2; colorectal cancer; COLORECTAL-CANCER; MICRORNA BIOGENESIS; SIGNALING PATHWAY; DRUG-RESISTANCE; BREAST-CANCER; 5-FLUOROURACIL; THERAPIES;
D O I
10.2147/OTT.S159093
中图分类号
Q81 [生物工程学(生物技术)]; Q93 [微生物学];
学科分类号
071005 ; 0836 ; 090102 ; 100705 ;
摘要
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.
引用
收藏
页码:1757 / 1765
页数:9
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