Inhibition of circ_0127646 Enhanced the Cisplatin Sensitivity in Osteosarcoma Cells via miR-22/KAT6B Axis

Effective chemotherapy could improve the survival rate of patients with osteosarcoma (OS), but the efficacy of such treatments is often compromised by the development of drug resistance. Circular RNAs are known to exert pivotal regulatory functions in the chemoresistance of multiple tumor cells. The present study was designed to investigate the role and underlying mechanism of circ_0127646 in modulating the chemosensitivity of OS cells to cisplatin. We observed a marked upregulation of circ_0127646 in OS cell lines (HOS, MG63, U2OS, and OS9901) following cisplatin treatment. Silencing of circ_0127646 by a small interfering RNA (si-circ) enhanced cisplatin-induced apoptosis and diminished clonogenic capacity in MG63 and OS9901 cells. Moreover, the sensitizing effect of si-circ to cisplatin in OS cells was counteracted by si-miR-22. Inhibition of circ_0127646 augmented the suppressive effect of miR-22 on KAT6B expression, leading to a reduction in the expression levels of some cytokines, including S100A8, S100A9, PDGF, and VEGF. This reduction, in turn, inhibited the activation of PI3K/Akt/mTOR signaling pathway, thereby sensitizing OS cells to cisplatin. Collectively, our findings indicated that inhibition of circ_0127646 could enhance the chemosensitivity of OS cells to cisplatin via miR-22/KAT6B axis. Circ_0127646 might serve as a prognostic biomarker for cisplatin-based therapies and a potential therapeutic target in OS.