title: MicroRNA-93-5p increases multidrug resistance in human colorectal carcinoma cells by downregulating cyclin dependent kinase inhibitor 1A gene expression.
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, thein vitrodrug 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.
authors.affiliation: Department of Colorectal and Anal Surgery, First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi 530021, P.R. China.
authors.forename: Shi-Jun
authors.initials: SJ
authors.lastname: Wang
authors.affiliation: Department of Colorectal and Anal Surgery, First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi 530021, P.R. China.
authors.forename: Yun-Fei
authors.initials: YF
authors.lastname: Cao
authors.affiliation: Department of Colorectal and Anal Surgery, First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi 530021, P.R. China.
authors.forename: Zu-Qing
authors.initials: ZQ
authors.lastname: Yang
authors.affiliation: Department of Colorectal and Anal Surgery, First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi 530021, P.R. China.
authors.forename: Zhi-Yuan
authors.initials: ZY
authors.lastname: Jiang
authors.affiliation: Department of Colorectal and Anal Surgery, First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi 530021, P.R. China.
authors.forename: Bin
authors.initials: B
authors.lastname: Cai
authors.affiliation: Experimental Department, Affiliated Tumor Hospital of Guangxi Medical University, Nanning, Guangxi 530021, P.R. China.
authors.forename: Jiao
authors.initials: J
authors.lastname: Guo
authors.affiliation: Department of Colorectal and Anal Surgery, First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi 530021, P.R. China.
authors.forename: Sen
authors.initials: S
authors.lastname: Zhang
authors.affiliation: Department of Colorectal and Anal Surgery, First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi 530021, P.R. China.
authors.forename: Xiao-Long
authors.initials: XL
authors.lastname: Zhang
authors.affiliation: Department of Colorectal and Anal Surgery, First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi 530021, P.R. China.
authors.forename: Feng
authors.initials: F
authors.lastname: Gao
keywords: colorectal carcinoma; cyclin dependent kinase inhibitor 1A; microRNA-93; multidrug resistance; multidrug resistance protein 1