IL-32/NFκB/miR-205 loop sustains the high expression of IL-32 and enhances the motility of cervical cancer cells.

Abstract

Human papillomavirus (HPV) infection is a major contributor to cervical cancer. Persistent HPV infection can trigger the expression of IL-32, yet the precise role of IL-32 in the occurrence and development of cervical cancer remains elusive. To investigate this, qRT‒PCR and western blotting were utilized to measure the mRNA and protein expression levels; bioinformatics analysis was used to screen differentially expressed miRNAs; wound healing and transwell assays were conducted to evaluate cell migration and invasion capabilities. Comparative analysis revealed significantly elevated IL-32 expression in cervical cancer tissues and cell lines compared to control groups. In SiHa and/or HeLa, overexpression of IL-32 and IL-32 exposure markedly upregulated miR-205, whereas its knockdown resulted in a substantial downregulation of miR-205. Furthermore, miR-205 also could significantly regulate the expression of IL-32 in HeLa and SiHa cells. Upregulation and downregulation of IL-32 led to a significant increase or decrease in NFκB expression, respectively. Treatment with BAY11-7082 (an NFκB inhibitor) notably decreased miR-205 expression but had no effect on IL-32 levels. qRT‒PCR and western blotting analyses demonstrated that both overexpression and underexpression of IL-32 and miR-205 significantly enhanced or reduced MMP2 and MMP9 expression in cervical cancer cells, respectively. Knockdown of IL-32 significantly inhibited the migration and invasion of HeLa and SiHa; conversely, treatment with rIL-32α and rIL-32γ notably promoted their migration and invasion. In brief, IL-32 is highly expressed via the formation of a positive regulatory loop with NFκB/miR-205, contributing to the persistence of inflammation and promoting the progression of cervical cancer.