Resistance to chemotherapy drugs is a major factor affecting the surgical outcome and prognosis of osteosarcoma patients. Circular RNAs (circRNAs) play an important role in tumor resistance to chemotherapy. In the present study, we aimed to investigate the role and mechanism of circRNA circ-chitinase 3-like 1.2 (CHI3L1.2) in resistance to cisplatin chemotherapy in osteosarcoma. We found that circ-CHI3L1.2 levels were higher in cisplatin-resistant cells than in their parent cells. circ-CHI3L1.2 knockdown decreased the half-maximal inhibitory concentration (IC50) of cisplatin and the expression levels of P-glycoprotein (P-gp), multidrug-resistance protein 1 (MRP1), and glutathione-S-transferase Pi1 (GSTP1), and promoted apoptosis of cisplatin-resistant osteosarcoma cells. In addition, circ-CHI3L1.2 knockdown induced mesenchymal to epithelial transition (MET) and suppressed cell migration and invasion. The competitive endogenous RNA (ceRNA) mechanism indicated that circ-CHI3L1.2 targets the micro-RNA (miR)-340-5p-lysophosphatidic acid acyltransferase β (LPAATβ) axis, and inhibition of miR-340-5p alleviates the effect of circ-CHI3L1.2 knockdown. In conclusion, circ-CHI3L1.2 levels were increased in cisplatin-resistant osteosarcoma cells and circ-CHI3L1.2 knockdown sensitized cisplatin-resistant osteosarcoma cells to cisplatin through the miR-340-5p-LPAATβ axis.
Keywords: Circ-CHI3L1.2; Cisplatin resistance; Competitive endogenous RNA; LPAATβ; miR-340-5p.
© 2021. Japan Human Cell Society.