Downregulation of Circ-CEP128 Enhances the Paclitaxel Sensitivity of Cervical Cancer Through Regulating miR-432-5p/MCL1.

Abstract

Chemoresistance is a common problem in cancer treatment, and circular RNA (circRNA) has been found to be associated with the progression of chemoresistance in cancer. However, the role and mechanism of circRNA centrosomal protein 128 (circ-CEP128) in the chemoresistance of cervical cancer (CC) are still unclear. The expression of circ-CEP128, microRNA (miR)-432-5p, and myeloid cell leukemia-1 (MCL1) was measured by quantitative real-time PCR. The paclitaxel resistance of cells was assessed using MTT assay. Cell proliferation, apoptosis, migration, and invasion were determined using MTT assay, colony formation assay, flow cytometry, and transwell assay. The protein levels of metastasis markers and MCL1 were examined using western blot analysis. Mice xenograft models were constructed to assess the effect of circ-CEP128 silencing on CC tumor growth and paclitaxel sensitivity. The interaction between miR-432-5p and circ-CEP128 or MCL1 was confirmed by dual-luciferase reporter assay and RIP assay. Circ-CEP128 had highly expression in CC tumor tissues and cells. Silencing of circ-CEP128 could enhance the paclitaxel sensitivity of CC cells by decreasing cell growth, migration, and invasion. Also, knockdown of circ-CEP123 reduced CC tumor growth and promoted the paclitaxel sensitivity of CC tumors. MiR-432-5p was found to be sponged by circ-CEP128, and its inhibitor could reverse the promoting function of circ-CEP128 silencing on the paclitaxel sensitivity of CC cells. Additionally, MCL1 was a target of miR-432-5p, and circ-CEP128 could sponge miR-432-5p to regulate MCL1. Besides, overexpressed MCL1 also could reverse the enhancing effect of miR-432-5p on the paclitaxel sensitivity of CC cells. In conclusion, the present study showed that circ-CEP128 silencing could increase the paclitaxel sensitivity of CC by regulating the miR-432-5p/MCL1 axis.