Long noncoding RNA OIP5‐AS1 causes cisplatin resistance in osteosarcoma through inducing the LPAATβ/PI3K/AKT/mTOR signaling pathway by sponging the miR‐340‐5p

Abstract The abnormal expression of long noncoding RNAs (lncRNAs) plays an important role in the regulation of human cancer progression and drug resistance. The lncRNA OPI5‐AS1 is a crucial regulator in some cancers; however, its role in cisplatin resistance of osteosarcoma remains unclear. We found that OIP5‐AS1 was significantly upregulated in cisplatin‐resistant (CR) osteosarcoma cells MG63‐CR and SaOS2‐CR compared with the corresponding parental cells. OIP5‐AS1 silencing suppressed cell growth in vitro and in vivo, and promoted apoptosis of MG63‐CR and SaOS2‐CR cells, indicating that knockdown of OIP5‐AS1 significantly decreased cisplatin resistance in MG63‐CR and SaOS2‐CR cells. This conclusion was supported by the decreased expression of the drug resistance‐related factors multidrug resistance‐associated protein 1 (MRP1) and P‐glycoprotein (P‐gp) upon OIP5‐AS1 silencing. In addition, OIP5‐AS1 downregulation suppressed the PI3K/AKT/mTOR signaling pathway. Importantly, we demonstrated that OIP5‐AS1 functions as a competing endogenous RNA of miR‐340‐5p and regulates the expression of lysophosphatidic acid acyltransferase (LPAATβ), which is a target of miR‐340‐5p . Moreover, downregulation of miR‐340‐5p partly reversed the inhibitory effect of OIP5‐AS1 knockdown on the PI3K/AKT/mTOR pathway and therefore counteracted cisplatin resistance in MG63‐CR and SaOS2‐CR cells. In conclusion, OIP5‐AS1 causes cisplatin resistance in osteosarcoma through inducing the LPAATβ/PI3K/AKT/mTOR signaling pathway by sponging the miR‐340‐5p . Our results contribute to a better understanding of the function and mechanism of OIP5‐AS1 in osteosarcoma cisplatin resistance.