Circular RNA circ_0004488 Increases Cervical Cancer Paclitaxel Resistance via the miR-136/MEX3C Signaling Pathway.

Abstract

Circular RNAs have been proven to play a pivotal role in cervical cancer development, progression, and treatment resistance. However, it is unclear how these RNAs influence chemoresistance in cervical cancer, particularly cancer stem cell (CSC)-like properties. In this study, we found that circRNA circ_0004488 was highly expressed in CSC-enriched subsets of cervical cancer cell lines. The expression of circ_0004488 was upregulated in cervical cancer cells that were resistant to paclitaxel. When circ_0004488 expression was high, the prognosis was poor. Specifically, we discovered that knocking down circ_0004488 greatly decreased the development of cervical cancer cells in vivo by decreasing cell proliferation, invasion, and sphere formation. By blocking cir_0004488, cervical cancer cells become more sensitive to paclitaxel. In cervical cancer cells, circ_0004488 acted as a microRNA-136 (miR-136) sponge, increasing the expression of MEX3C (a direct target gene of miR-136) using dual-luciferase reporter assays. Moreover, MEX3C downregulation significantly reduced cell proliferation, invasion, sphere formation, and paclitaxel resistance. In conclusion, circ_0004488 was shown to induce CSC-like features and paclitaxel resistance through the miR-136/MEX3C axis. Therefore, circ_0004488 might be a good therapeutic target for treating cervical cancer.