Down-regulation of miR-377 contributes to cisplatin resistance by targeting XIAP in osteosarcoma

X.-G. Liu, J. Xu, F. Li, M.-J. Li, T. Hu

Department of Head and Neck and Neurosurgery, Hubei Cancer Hospital, Wuhan, Hubei, China. xujian200903@sina.cn

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• Oncology

OBJECTIVE: Chemoresistance is one of the obstacles for effective treatment of cancers, and recent evidence has shown that microRNAs play critical roles in drug resistance. In this study, we investigated the effect of miR-377 on cisplatin resistance in osteosarcoma (OS).

PATIENTS AND METHODS: Tumor tissues from chemoresistant and control OS patients were subjected to Real-time polymerase chain reaction (PCR) to assess miR-377 expression. The effect and mechanism of miR-377 on cisplatin resistance were assessed using Cell Counting Kit (CCK) 8, flow cytometry, Western blot, and luciferase assays in cisplatin-resistant OS cells lines.

RESULTS: Down-regulation of miR-377 was found in chemoresistant OS tissues and cisplatin-resistant OS cell lines. Overexpression of miR-377 re-sensitizes cisplatin resistant OS cells to cisplatin-induced caspase-3 dependent apoptosis. MiR-377 directly represses X-linked inhibitor of apoptosis protein (XIAP) expression through binding to its 3’ untranslated region (UTR) of mRNA. Overexpression of XIAP partially cancelled the cisplatin-sensitizing effect of miR-377.

CONCLUSIONS: These data uncovered an essential function of miR-377/XIAP signaling axis in regulating cisplatin resistance of OS. MiR-377 may have potential therapeutic values in tackling OS chemoresistance.

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