2. Academic Validation
  3. miR-338-3p confers 5-fluorouracil resistance in p53 mutant colon cancer cells by targeting the mammalian target of rapamycin

miR-338-3p confers 5-fluorouracil resistance in p53 mutant colon cancer cells by targeting the mammalian target of rapamycin

  • Exp Cell Res. 2017 Nov 15;360(2):328-336. doi: 10.1016/j.yexcr.2017.09.023.
Jia Han 1,  Jie Li 2,  Kaijie Tang 1,  Huahua Zhang 3,  Bo Guo 1,  Ni Hou 4,  Chen Huang 5
Affiliations

Affiliations

  • 1 Department of Cell Biology and Genetics, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, Xi'an, China.
  • 2 Department of General Surgery, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.
  • 3 Department of Cell Biology and Genetics, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, Xi'an, China; Medical College, Yan'an University, Yan'an, China.
  • 4 Department of Cell Biology and Genetics, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, Xi'an, China. Electronic address: houni@mail.xjtu.edu.cn.
  • 5 Department of Cell Biology and Genetics, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, Xi'an, China; Key Laboratory of Shaanxi Province for Craniofacial Precision Medicine Research, College of Stomatology, Xi'an Jiaotong University, Xi'an, China. Electronic address: hchen@mail.xjtu.edu.cn.
PMID: 28928082 DOI: 10.1016/j.yexcr.2017.09.023
Abstract

Evidence demonstrate that p53 mutations and MicroRNAs (miRs) are important components of 5-FU resistance in colorectal Cancer (CRC). miR-338-3p has been reported associated with Cancer prognosis. However whether or not it influences chemotherapy sensitivity and the underlying mechanisms have not been elucidated. Here, three types of human colon Cancer cell lines, HT29 (mutant p53), HCT116 (wild-type p53), and HCT116 p53-/- (deficient p53), were treated with 5-FU. We showed that expression of miR-338-3p was correlated with Apoptosis and 5-FU resistance in colon Cancer cells. Ectopic expression of miR-338-3p conferred resistance to 5-FU in HCT116 cells. Further experiments indicated that miR-338-3p mediated 5-FU resistance through down-regulation of mTOR expression. Moreover, inhibition of miR-338-3p in HT29 and HCT116 p53-/- cells increased their sensitivity to 5-FU treatment. Furthermore, we detected Autophagy changes in our experiment because mTOR was known prominently regulating Autophagy and the competition between Autophagy and Apoptosis in response to 5-FU was a mechanism influencing 5-FU sensitivity. Our results reveal a critical and novel role of miR-338-3p in the correlation of 5-FU resistance with p53 status. Moreover, the miR-338-3p inhibitor has the potential to overcome 5-FU resistance in p53 mutant colon Cancer cells.

Keywords

5-FU resistance; Colon cancer cell; mTOR; miR-338-3p; p53.

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