The mechanisms underlying oxaliplatin (OXA) resistance in colon cancer cells are not fully understood. MicroRNAs (miRNAs) play important roles in tumorigenesis and drug resistance. However, the relationship between miRNA and OXA resistance in colon cancer cells has not been previously explored. In this study, we utilized microRNA microarray analysis and real-time PCR to verify that miR-93, miR-191, miR-137, miR-181 and miR-491-3p were significantly down-regulated and that miR-96, miR-21, miR-22, miR-15b and miR-92 were up-regulated in both HCT-15/OXA and SW480/OXA cell lines. Blocking miR-137 caused a significant inhibition of OXA-induced cytotoxicity, therefore, miR-137 was chosen for further research. An in vitro cell viability assay showed that knockdown of miR-137 in HCT-15 and SW480 cells caused a marked inhibition of OXA-induced cytotoxicity. Moreover, we found that miR-137 was involved in repression of YBX1 expression through targeting its 3'-untranslated region. Furthermore, down-regulation of miR-137 conferred OXA resistance in parental cells, while over-expression of miR-137 sensitized resistant cells to OXA, which was partly rescued by YBX1 siRNA. The results of this study may aid the development of therapeutic strategies to overcome colon cancer cell resistance to OXA.
Keywords: Colon cancer; YBX1; drug resistance; miR-137.