MiR-20a-5p represses multi-drug resistance in osteosarcoma by targeting the KIF26B gene.

BACKGROUND:Chemoresistance hinders curative cancer chemotherapy in osteosarcoma (OS), resulting in only an approximately 20 % survival rate in patients with metastatic disease at diagnosis. Identifying the mechanisms responsible for regulating chemotherapy resistance is crucial for improving OS treatment. METHODS:This study was performed in two human OS cell lines (the multi-chemosensitive OS cell line G-292 and the multi-chemoresistant OS cell line SJSA-1). The levels of miR-20a-5p and KIF26B mRNA expression were determined by quantitative real-time PCR. KIF26B protein levels were determined by western blot analysis. Cell viability was assessed by MTT assay. Apoptosis was evaluated by flow cytometry. RESULTS:We found that miR-20a-5p was more highly expressed in G-292 cells than in SJSA-1 cells. Forced expression of miR-20a-5p counteracted OS cell chemoresistance in both cell culture and tumor xenografts in nude mice. One of miR-20a-5p's targets, kinesin family member 26B (KIF26B), was found to mediate the miR-20a-5p-induced reduction in OS chemoresistance by modulating the activities of the MAPK/ERK and signaling pathways. CONCLUSIONS:In addition to providing mechanistic insights, our study revealed that miR-20a-5p and KIF26B contribute to OS chemoresistance and determined the roles of these genes in this process, which may be critical for characterizing drug responsiveness and overcoming chemoresistance in OS patients.

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