The role of Connexin26 regulated by MiR-2114-3p in the pathogenesis of ovarian cancer.

ABSTRACT

OBJECTIVES: The purpose of our research was to determine the expression of Cx26 and miR-2114-3p, and their effects on proliferation, migration, and invasion in ovarian cancer and their mechanisms. MATERIALS AND METHODS: Transcriptome sequencing was performed and differentially expressed Cx26 was screened. The mRNA and protein levels of Cx26 in EOC and normal ovarian tissues were verified. The relationship between Cx26 levels and prognostics was analyzed. Cx26 Lentiviral vectors were constructed to detect its effect on ovarian cancer. WB verified that PI3K/AKT pathway was the possible signal pathway regulated by Cx26. The interaction between miR-2114-3p and Cx26 was detected by double luciferase reporter assay and qrt-PCR. CCK8, clone formation, transwell, and flow cytometry assays were conducted in cells transfected miR-2114-3p plasmids. The vivo experiment investigated the effects of Cx26 on subcutaneous tumor growth, PI3K expression, proliferation proteins Ki67 and PCNA. RESULTS: Cx26 was up-regulated in EOC tissue and cell lines, and was associated with poor prognosis of ovarian cancer, while miR-2114-3p was down-regulated in EOC cell lines. Cx26 was a direct target of miR-2114-3p. Cx26 overexpression and miR-2114-3p inhibition promoted the growth, motility, invasiveness, and S phase arrest of EOC cells. Additionally, Cx26 could activated PI3K pathway whatever in vivo and in vitro. CONCLUSIONS: Dysregulation of Cx26 is critical in EOC patients. Manipulation of this mechanism may influence the survival of EOC patients. MiR-2114-3p regulates the tumor-promoting activity of Cx26 in EOC. By inhibiting the PI3K pathway or knocking down Cx26 effectively inhibits tumor growth in EOC cells and Nude mouse model.