Abstract
Cisplatin resistance is a major challenge in cervical cancer (CC) chemotherapy. Growth arrest-specific 5 (GAS5) has been reported to be a tumour suppressor gene in CC. However, the mechanism of GAS5 in chemoresistance remains undetermined. Our research evaluated GAS5 expression in normal and CC tissues by qPCR and in situ hybridization (ISH). Statistical analysis was conducted to analyse the association of GAS5 expression with survival. Biochemical methods were used to screen upstream and downstream regulators of GAS5. Then, interactions were confirmed by ChIP, RNA pull-down, RNA immunoprecipitation (RIP), dual-luciferase reporter and real-time PCR assays. The cisplatin sensitivity of GAS5-overexpressing CC cells was demonstrated in vitro and in vivo. The results showed that low GAS5 expression was correlated with poor overall survival. Mechanistically, GAS5 was transcriptionally modulated by P-STAT3 and served as a competing endogenous RNA (ceRNA) of miR-21 to indirectly affect cisplatin sensitivity through PDCD4 regulation in CC cells. Animal studies confirmed that GAS5 enhanced cisplatin sensitivity and promoted PDCD4 expression in vivo. GAS5 was regulated by P-STAT3 and affected the sensitivity of CC to cisplatin-based chemotherapy through the miR-21/PDCD4 axis. This result may provide new insight into cisplatin-based therapy.