Effects of miR-214 on cervical cancer cell proliferation, apoptosis and invasion via modulating PI3K/AKT/mTOR signal pathway.

ABSTRACT

OBJECTIVE: PI3K/AKT/mTOR pathway plays important roles in tumor pathogenesis. mTOR is up-regulated and miR-214 is down-regulated in cervical can-*cers. This study investigated whether miR-214 regulated mTOR expression and affected cervical cancer cell proliferation, apoptosis or invasion. PATIENTS AND METHODS: Cervical cancer tissues were collected in parallel with normal epithelium for measuring the expression of miR-214 and mTOR. Dual luciferase expression assay was performed to evaluate the targeted relationship between miR-214 and mTOR. In vitro cultured SiHa cells were treated with miR-214 mimic or si-mTOR followed by measuring mTOR, p-mTOR and Bcl-2 expression. Cell apoptosis, proliferation and invasion were measured by flow cytometry and transwell assay. RESULTS: Bioinformatics analysis showed targeted binding sites between miR-214 and 3'-UTR of mTOR mRNA. Dual luciferase reporter assay confirmed this regulatory relationship between miR-214 and mTOR mRNA. Compared to normal cervical epithelium, cancer tissues had lower expression of miR-214 and higher mTOR, both of which were correlated with TNM stage and tissue pathology grade. Compared to Ect1/E6E7 cells, SiHa cells had lower level of miR-214 and higher mTOR/p-mTOR and Bcl-2 expression. Transfection of miR-214 mimic or si-mTOR significantly decreased mTOR/p-mTOR or Bcl-2 expression, inhibited cell proliferation or invasion, and enhanced cell apoptosis. CONCLUSIONS: miR-214 down-regulation plays a role in elevating mTOR expression and in facilitating cervical cancer pathogenesis. Over-expression of miR-214 inhibits cervical cancer cell proliferation or invasion, and facilitates apoptosis via targeted inhibition of mTOR expression.