Upregulation of kazrin F by miR-186 suppresses apoptosis but promotes epithelial-mesenchymal transition to contribute to malignancy in human cervical cancer cells

Objective：Previous studies have identified that kazrin is a constituent of desmosome and influences intercellular adhesion,growing development and morphology.We previously cloned another new isoform,kazrin F and found that it has anti-apoptotic effects on human glioma cell line.To further explore whether kazrin F is involved in tumorigenesis,we investigated its expression and role in cervical cancer（CC） cells.Methods：The role of kazrin F and miR-186 in CC was determined by 3-（4,5-dimethylthiazol-2-yl）-2,5-diphenyltetrazolium bromide（MTT） assay,colony formation,transwell,and apoptosis assays.Using enhanced green fluorescent protein（EGFP） reporter assays,reverse transcription-quantitative polymerase chain reaction（RT-qPCR） and western blot analysis,we identified kazrin F post-transcriptional regulation by miR-186.Results：We demonstrate that kazrin F is highly expressed in CC tissues compared with the adjacent noncancerous tissues and promotes cell proliferation,colony formation,migration and invasion in HeLa and C33 A cells by suppressing apoptosis and facilitating epithelial-to-mesenchymal transition（EMT）.Furthermore,miR-186 was confirmed as a regulator of kazrin F dysregulation.An EGFP reporter assay proved that miR-186 directly targets the 3＇-untranslated region（3＇UTR） of kazrin F and downregulates its expression,and miR-186 expression showed an inverse correlation with kazrin F levels in CC tissues.In addition,overexpression of miR-186 suppressed the malignant behaviors of CC cells.The ectopic expression of kazrin F rescued the inhibitory effects of miR-186.Conclusions：Our findings indicate that the upregulation of kazrin F due to downregulated miR-186 levels contributes to malignancy,and highlight the significance of kazrin F in CC tumorigenesis.