Long non-coding RNA ROR regulated ABCB1 to induce cisplatin resistance in osteosarcoma by sponging miR-153-3p

F.-H. Cheng, Z.-S. Zhao, W.-D. Liu

Department of Orthopedics, Weinan Central Hospital, Shaanxi, China. chilanlusw5@126.com

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• Oncology

OBJECTIVE: Osteosarcoma (OS) is a common cancer among adolescences worldwide. Cisplatin is widely used to treat cancer, but many patients acquire chemoresistance over time. LncRNA regulator of reprogramming (ROR) has been reported to be associated with many malignancies, including OS. However, the function of ROR in cisplatin resistance and the biological mechanism of ROR remain unclear in OS.

PATIENTS AND METHODS: The levels of ROR, miR-153-3p, and ABCB1 in cisplatin-resistant OS tissues and cells were detected by qRT-PCR and/or Western blot assay. The interactions of miR-153-3p, ROR, and ABCB1 were predicted by miRcode Tools and StarBase v2.0 online database, respectively, and validated by Dual-Luciferase reporter assay. The cell viability in different concentrations of DDP, cell proliferative capacity, migrated cells, and invaded cells were detected by MTT assay and transwell assay, respectively.

RESULTS: The levels of ROR and ABCB1 were both drastically increased, and miR-153-3p was apparently decreased in relapsed OS tissues, MG63/DDP, and U2OS/DDP cells. MiRcode Tools and StarBase v2.0 predicted that miR-153-3p had complementary sequences with ROR and ABCB1 3’UTR, and following Dual-Luciferase reporter assay validated that miR-153-3p was a direct target of ROR and ABCB1. Moreover, ABCB1 overexpression alleviated the inhibitory effects on cell viability in different concentrations of DDP, cell proliferative capacity, migrated cells, and invaded cells in MG63/DDP and U2OS/DDP cells transfected with sh-ROR. ROR regulated ABCB1 expression in MG63/DDP and U2OS/DDP cells by sponging miR-153-3p.

CONCLUSIONS: We found that ROR or ABCB1 knockdown can increase the cisplatin sensitivity of MG63/DDP and U2OS/DDP cells. ROR contributed to cisplatin resistance in OS via miR-153-3p/ABCB1 axis, unraveling a new regulatory network of chemoresistance in cisplatin-resistant OS cells and may provide a therapeutic target for OS patients.

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