MicroRNA Profiling of Oxaliplatin-Resistant HCT116 Colorectal Cancer Cells

Abstract

Aim: To investigate the impact of oxaliplatin resistance on the cellular characteristics and miRNA expression pattern in colorectal cancer cells. Methods: A stable oxaliplatin-resistant colorectal cancer HCT116 cell line was established by exposure to increasing doses of oxaliplatin. Alterations in cytotoxicity, migration, invasion and tumorsphere formation were assessed by MTS assay, modified Boyden chamber assay, and colonosphere assay respectively. The miRNAome of the oxaliplatin-resistant HCT116 cells was analyzed using the TaqMan PCR Human miRNA array. Upregulated miRNAs from the PCR array were validated by real-time reverse transcription-quantitative PCR (RT-qPCR). Results: Oxaliplatin-resistant HCT116 cells exhibited higher migration, invasion and tumorsphere formation compared to parental oxaliplatin-sensitive HCT116 cells. The oxaliplatin-resistant cells showed a distinct miRNA expression profile compared to the parental cells. The expression of miR-601, miR-222, miR-202 and miR-25 were verified by RT-qPCR to be increased in resistant cells. Bioinformatics analyses were used to identify potential target mRNAs of these 4 miRNAs. Conclusion: Results presented in this study provide evidence that oxaliplatin-resistance induces phenotypic changes in colorectal cancer and alterations in miRNA expression. Functional studies on the miRNAs and their target mRNA may enable the discovery of functional pathways to chemoresistance in colorectal cancer.