MicroRNA‑93‑5p increases multidrug resistance in human colorectal carcinoma cells by downregulating cyclin dependent kinase inhibitor 1A gene expression

Wang,Shi‑Jun; Cao,Yun‑Fei; Yang,Zu‑Qing; Jiang,Zhi‑Yuan; Cai,Bin; Guo,Jiao; Zhang,Sen; Zhang,Xiao‑Long; Gao,Feng

doi:10.3892/ol.2016.5463

MicroRNA‑93‑5p increases multidrug resistance in human colorectal carcinoma cells by downregulating cyclin dependent kinase inhibitor 1A gene expression

Authors:
- Shi‑Jun Wang
- Yun‑Fei Cao
- Zu‑Qing Yang
- Zhi‑Yuan Jiang
- Bin Cai
- Jiao Guo
- Sen Zhang
- Xiao‑Long Zhang
- Feng Gao
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Affiliations: Department of Colorectal and Anal Surgery, First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi 530021, P.R. China, Experimental Department, Affiliated Tumor Hospital of Guangxi Medical University, Nanning, Guangxi 530021, P.R. China
Published online on: December 6, 2016 https://doi.org/10.3892/ol.2016.5463
Pages: 722-730
Copyright: © Wang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Multidrug resistance (MDR) impedes successful chemotherapy in colorectal carcinoma (CRC) and emerging evidence suggests that microRNAs (miRs) are involved in the development of MDR. In the present study, the role of miR‑93‑5p in the modulation of drug resistance in CRC was investigated using HCT‑8 and MDR HCT‑8/vincristine (VCR) cell lines. The results demonstrated upregulated expression of miR‑93‑5p and MDR protein 1 (MDR1) in HCT‑8/VCR cells, compared with the parental HCT‑8 cells. Furthermore, cyclin‑dependent kinase inhibitor 1A (CDKN1A) was identified as a potential target of miR‑93‑5p using miR target analysis tools, including PicTar, TargetScan and miRanda. In addition, inhibition of miR‑93‑5p expression in HCT‑8/VCR cells markedly downregulated MDR1 gene expression, upregulated CDKN1A gene expression and induced cell cycle arrest in G1. Conversely, the overexpression of miR‑93‑5p in HCT‑8/VCR cells upregulated MDR1 gene expression, downregulated CDKN1A gene expression and promoted G1/S transition. Furthermore, the in vitro drug sensitivity assay performed suggested that downregulation of miR‑93‑5p enhanced the sensitivity of HCT‑8/VCR cells to VCR, while the upregulation of miR‑93‑5p decreased the sensitivity of HCT‑8 cells to VCR. In conclusion, the results of the present study suggest that miR‑93‑5p serves a role in the development of MDR through downregulating CDKN1A gene expression in CRC.

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