Charged multivesicular body protein 4C promotes the progression of cervical cancer through the HPV E6/miR 543 axis

Abstract

Charged multivesicular body protein 4C (CHMP4C), as a subunit of endosomal sorting complex required for transport III, is important for the abscission checkpoint in cell division, preventing premature cell division and genetic damage. The present study aimed to assess the role of CHMP4C in cervical cancer and the associated mecha nisms. The levels of CHMP4C in normal and cervical cancer tissues were detected by immunohistochemistry. The MTT assay, apoptosis, wound healing assay, and cell invasion assay were performed. Western blotting was performed to analyze the level of cancer related proteins following CHMP4C downregulation and the CHMP4C expression following E6 downregulation and miR 543 upregulation. The transfec tion effectiveness of siRNA, plasmid, and miRNA mimic as well as the expression of miR 543 after silencing E6 were assessed by RT PCR. The dual luciferase reporter assay was used to demonstrate a connection site between CHMP4C and miR 543. The results demonstrated that CHMP4C expression in cervical cancer tissues was significantly higher than that in normal tissues. Furthermore, downregulation of CHMP4C expression significantly reduced the proliferation, migra tion and invasion of cervical cancer cells and significantly increased the rate of apoptosis compared to the si scramble group. Comparison with the si scramble group, silencing CHMP4C expression also significantly reduced the expression of Bcl2, Bcl xL and Survivin, and was associated with a signif icant increase in Caspase 7 expression. After the knockdown of human papillomavirus (HPV) encoded E6, in comparison to the si scramble group, microRNA (miR) 543 expression was significantly elevated and CHMP4C expression signifi cantly decreased. Moreover, a connection site was detected between miR 543 and CHMP4C. These findings indicate that CHMP4C accelerates the tumorigenesis and progression of cervical cancer through the HPV E6/miR 543 axis.