Circular RNA hsa_circ_00027220-induced regulation of Yes-associated protein promotes platinum resistance in oral squamous cell carcinoma: implications for verteporfin therapy

Abstract

Abstract Purpose: Oral squamous cell carcinoma (OSCC) significantly impacts public health with its high occurrence and grim outcomes. Platinum resistance complicates OSCC treatment. Yes-associated protein (YAP) plays a key role in OSCC development, while circular RNA (circRNA) influences microRNA activity, contributing to chemoresistance in cancers. Yet, how circRNA affects YAP expression in OSCC is unclear. Methods: We examined the expression of YAP in 21 newly diagnosed OSCC cases using immunohistochemistry and quantitative polymerase chain reaction (qPCR). Cisplatin-resistant OSCC cell lines were established for further investigation. A luciferase reporter system, RNA pull-down assay, and RNA fluorescence in situ hybridization (FISH) assay were utilized to demonstrate that circRNA hsa_circ_0002722 (circ_0002722) could bind to microRNA-1305 (miR-1305). The synergistic effects of combined cisplatin and verteporfin (a YAP inhibitor) treatment were evaluated using SynergyFinder. We also developed subcutaneous tumorigenicity graft models to validate our findings in an in vivo setting. Results: Here, we found that YAP and circ_0002722 were upregulated in platinum-resistant OSCC tissues. Circ_0002722 acted as a regulator of miR-1305, influencing YAP expression and thereby mediating platinum sensitivity. In vivo experiments corroborated the synergistic effects of cisplatin and verteporfin in combating platinum resistance. Therefore, targeting YAP is a promising therapeutic strategy for addressing platinum resistance in OSCC, with circ_0002722 serving as a potential therapy target and valuable diagnostic marker. Conclusions: These findings provide novel insights into the underlying mechanisms of platinum resistance and suggest new avenues for developing effective treatment approaches in OSCC.