Circ_0076305 regulates cisplatin resistance of non-small cell lung cancer via positively modulating STAT3 by sponging miR-296–5p

Aims: Circular RNAs (circRNAs) acted as key regulators in the development of various human tumors. Our present study aimed to investigate the role and molecular mechanism of circ_0076305 in regulating cisplatin (DDP) resistance of non-small cell lung cancer (NSCLC). Main methods: Using RT-qPCR, the expressions of circ_0076305 in NSCLC tissues and cells (A549, H1650, A549/DDP, H1650/DDP) were measured. Through loss-of-function and overexpression experiments, the role of circ_0076305 in DDP resistance of NSCLC was verified. Inhibitory rate and IC50 for DDP were detected using MTT method after DDP treatment. Western blotting was performed to evaluate protein levels of P-gp and MRP1. The bindings between circ_0076305 and miR-296–5p, as well as miR-296–5p and STAT3 were validated by bioinformatics, CircRIP, Pearson's correlation analysis and luciferase report vector assays. Key findings: Circ_0076305 was upregulated in NSCLC, and more significantly elevated in DDP-resistant NSCLC tissues and cells. Further experiments discovered that circ_0076305 could regulate DDP resistance of NSCLC cells via binding to miR-296–5p. Directly targeted by miR-296–5p, STAT3 hindered the miR-296-5p-induced suppression on DDP resistance. Finally, the expression of circ_0076305 was found to have positive correlation with STAT3, and circ_0076305 was validated to regulate STAT3 via targeting miR-296–5p. Significance: Our present study illustrated that circ_0076305 regulated STAT3 expression and DDP resistance of NSCLC cells via sponging miR-296–5p. These results suggested knockdown of circ_0076305 might provide an effective approach for NSCLC treatment strategy.