miR-122 Targets X-Linked Inhibitor of Apoptosis Protein to Sensitize Oxaliplatin-Resistant Colorectal Cancer Cells to Oxaliplatin-Mediated Cytotoxicity.
BACKGROUND/AIMS
Although oxaliplatin is one of the most effective chemotherapeutic drugs used to treat colorectal cancer (CRC), long-term administration usually induces acquired drug resistance during the course of treatment. Thus, there is an urgent need to explore novel strategies to improve the efficiency of cancer therapy. The aim of this study was to explore the effect of microRNA-122 (miR-122) on reversing oxaliplatin resistance in CRC.


METHODS
The expression of miR-122 in CRC cells was examined by quantitative reverse transcriptase real-time PCR. The cytotoxicity of oxaliplatin against CRC cells was evaluated by Cell Counting Kit-8 assays. Mitochondrial membrane potentials and cell apoptotic rates were measured by flow cytometry. Cellular protein expression and interactions were detected by western blot and co-immunoprecipitation.


RESULTS
Established oxaliplatin-resistant SW480 and HT29 cells (SW480/OR and HT29/OR) expressed significantly higher levels of X-linked inhibitor of apoptosis protein (XIAP) and lower levels of miR-122 compared with normal SW480 and HT29 cells, respectively. Our results showed that the downregulation of miR-122 was responsible for the overexpression of XIAP in these oxaliplatin-resistant CRC cells. We then found that the recovery of miR-122 expression can sensitize SW480/OR and HT29/OR cells to oxaliplatin-mediated apoptosis through the inhibition of XIAP expression.


CONCLUSION
Upregulation of XIAP in CRC cells is responsible for the acquired resistance to oxaliplatin. Furthermore, miR-122 reversed oxaliplatin resistance in CRC by targeting XIAP.
['Hua|Yongqiang|Y|', 'Zhu|Yaodong|Y|', 'Zhang|Jijie|J|', 'Zhu|Zhenfeng|Z|', 'Ning|Zhouyu|Z|', 'Chen|Hao|H|', 'Liu|Luming|L|', 'Chen|Zhen|Z|', 'Meng|Zhiqiang|Z|']
D000970:Antineoplastic Agents D017209:Apoptosis D045744:Cell Line, Tumor D015179:Colorectal Neoplasms D019008:Drug Resistance, Neoplasm D015972:Gene Expression Regulation, Neoplastic D019073:HT29 Cells D006801:Humans D035683:MicroRNAs D000077150:Oxaliplatin D015854:Up-Regulation D051636:X-Linked Inhibitor of Apoptosis Protein
miR-122 Colorectal cancer Oxaliplatin resistance XIAP