Overcoming cisplatin resistance in osteosarcoma through the miR-199a-modulated inhibition of HIF-1 α.

In this study, we demonstrated that miR-199a is expressed at low levels in osteosarcoma cells and patient samples. By the selection and establishment of cisplatin resistant osteosarcoma cell line, we observed a correlation between miR-199a and cisplatin resistance in osteosarcoma cells: resistant cells exhibit attenuated miR-199a expressions and exogenous overexpression of miR-199a sensitizes osteosarcoma cells to cisplatin. Moreover, we identified HIF-1α as a direct target of miR-199a. Intriguingly, cisplatin resistant osteosarcoma cells display significantly elevated HIF-1α expression under hypoxia. We report here overexpression of miR-199a re-sensitizes cisplatin resistant cells to cisplatin through inhibition of HIF-1α in vitro and in vivo Finally, by analyzing the clinical osteosarcoma patient samples, we demonstrate a reverse correlation between miR-199a and HIF-1α mRNAs. Our study will provide mechanisms for the microRNAs-mediated anti-cancer therapy and miR-199a may be considered a promising therapeutic agent for osteosarcoma patients who fail to respond to conventional chemotherapy. PMID: 28442599 [PubMed - as supplied by publisher]
Source: Bioscience Reports - Category: Biomedical Science Authors: Tags: Biosci Rep Source Type: research