Long Non-Coding RNA OIP5-AS1 Knockdown Enhances CDDP Sensitivity in Osteosarcoma via miR-377-3p/FOSL2 Axis.

BACKGROUND

Drug resistance is one of big obstacles for the treatment of tumor. Long non-coding RNA Opa-interacting protein 5-antisense RNA 1 (OIP5-AS1) was identified to involve in drug resistance. In this research, the effects of OIP5-AS1 on cisplatin (CDDP) resistance in osteosarcoma (OS) were mainly investigated.

METHODS

The levels of OIP5-AS1, microRNA-377-3p (miR-377-3p), and FOS like 2 (FOSL2) were measured by quantitative real-time polymerase chain reaction. The inhibitory concentration 50 (IC) value of CDDP, cell viability and apoptotic rate was evaluated through Cell Counting Kit-8 and flow cytometry assays, respectively. The levels of multidrug resistance-associated protein 1 (MRP1), P-glycoprotein, B-cell lymphoma 2, Bcl2-associated X, cleaved-caspase-3, and FOSL2 were detected by Western blot assay. The interaction between miR-377-3p and OIP5-AS1 or FOSL2 was verified by Dual-Luciferase Reporter and RNA Immunoprecipitation assays. The function of OIP5-AS1 was detected by a xenograft tumor model in vivo.

RESULTS

OIP5-AS1 and FOSL2 were up-regulated, while miR-377-3p was down-regulated in CDDP-resistant OS tissues and cells. OIP5-AS1 silencing inhibited cell viability and the IC value of CDDP, and promoted apoptotic rate in CDDP-resistant OS cells. Mechanically, OIP5-AS1 was verified as a sponge to miR-377-3p and FOSL2 was a target of miR-377-3p. Moreover, OIP5-AS1 knockdown repressed OS tumor growth and enhanced CDDP sensitivity of OS in vivo.

CONCLUSION

OIP5-AS1 positively modulated FOSL2 expression to decrease CDDP sensitivity in OS by sponging miR-377-3p.