Abstract:

Objective To evaluate the effect of miR-182 in radioresistant cervical caner cells and its probable regulative mode. Methods HeLa cell lines and SiHa cell lines were induced by fractionated dose irradiation, respectively, once a week at 4 Gy (HR4 group and SR4 group) and once a week at 6 Gy (HR6 group and SR6 group). Expression of HES1 and miR-182 in 4 radiation resistant cells were detected using RT-qPCR and Western blotting.The expression levels of epithelial-mesenchymal transition-(EMT-) related factors (E-cadherin, Slug)  were detected after down-regulation of miR-182 in selected radioresistant HR6 cells, and the capability of invasion and migration of HR6 cells was measured using the transwell assay. Additionally, we separately knocked down miR-182 or HES1 and investigated their ralationship. Results HES1 were significantly reduced in HeLa and SiHa cells after radiation, while miR-182 were significantly increased. Levels of miR-182 were diverse in different radioresistant cells. Knockdown of miR-182 signifi-cantly increased E-cadherin, decreased Slug in HR6 HeLa cells, and silenced their migration and invasion. The expression of HES1 in HR6 cells was increased after miR-182 knockdown,while the knockdown of HES1 did not affect miR-182. Conclusions Silencing miR-182 can effectively inverse EMT and inhibit migration and invasion by radioresistant cervical cancer cells. miR-182 may exert these effects by regulating the expression of HES1.

Key words: Cervical neoplasms, Radioresistance, miR-182, HES1, Epithelial-mesenchymal transition, Migration