MIR-501 IS UPREGULATED IN CERVICAL CANCER AND PROMOTES CELL PROLIFERATION, MIGRATION AND INVASION BY TARGETING CYLD

Abstract

Background: Cervical cancer is the common gynecological deadly malignancy worldwide. Here we attempted to evaluate the effects and mechanisms of microRNA-501-5p (miR-501) on the cell proliferation, migration, in vasion and the clinical significance in the cervical cancer. Methods: Cervical cancer HeLa cells were transfected with miR-501 mimic or inhibitor or siRNA against Cylindromatosis (CYLD) using Lipofectamine 2000. miR-501 expression was assessed in HeLa cells and cervical cancer specimens by real-time qRT-PCR. The functional roles of miR-501 were determined by CCK-8, colony formation, scratch wound healing and transwell assays. The apoptosis rate was detected by flow cytometry assay. CYLD, BCL-2, BAX, NF-κB p65 and phosphorylated p65 (p-p65) proteins were examined by Western blotting. CYLD expression was evaluated by immunohistochemistry in cervical cancer tissues. Results: miR-501 was upregulated, whereas CYLD protein was downregulated in cervical cancer tissues com pared to normal cervical tissues. miR-501 overexpression and CYLD protein downregulation were positively correlated with poor differentiation, tumor size, International Federation of Gynecology and Obstetrics (FIGO) stage and lymph node metastasis. CYLD was downregulated by miR-501 at both mRNA and protein levels in HeLa cells. miR-501 promoted cell proliferation, migration and invasion in cervical cancer, while inhibited the apoptosis. This is possibly due to the downregulation of CYLD and subsequent activation of NF-κB p65. Conclusions: miR-501 upregulation and CYLD downregulation are associated with the development and pro gression of cervical cancer. miR-501 promotes cervical cancer cell proliferation, migration and invasion possibly via downregulating CCYLD and subsequently activating NF-κB p65. miR-501 might be a potential therapeutic target for cervical cancer.