MiR-221 and miR-222 simultaneously target ARID1A and enhance proliferation and invasion of cervical cancer cells

OBJECTIVE: Increased miR-221 and miR-222 expression were found in cervical cancer. In this study, we investigated the regulative role of miR-221 and miR-222 on ARID1A and further studied their roles in proliferation and invasion of cervical cancer cells. MATERIALS AND METHODS: The expression of miR-221/222 and ARID1A were detected in cervical cancer tissues and normal cervical tissues. Then, human cervical cancer cell lines, including Hela and siHa cells were used for in vitro studies. The cells were transfected with miR-221 or miR-222 mimics alone or in combination with pcDNA3.1-ARID1A expression vector with mutant miR-221 and miR-222 binding sequence. Then, cell viability, cell cycle distribution and invasion were measured. RESULTS: MiR-221/222 were significantly up-regulated, while ARID1A was significantly downregulated in cervical cancer tissues. MiR-221 and miR-222 have nearly the same binding site in the 3'UTR of ARID1A and could suppress its expression at protein level. Functionally, miR-221 and miR-222 overexpression significantly increased cell viability, increased the proportion of cells in S phase and enhanced invasion of both Hela and siHa cells. In contrast, ARID1A overexpression abrogated these effects of miR-221 and miR-222. CONCLUSIONS: MiR-221 and miR-222 upregulation partly contribute ARID1A loss in cervical cancer. The miR-221/222-ARID1A axis can modulate proliferation and invasion of cervical cancer cells. These findings revealed a novel mechanism of ARID1A loss and a potential therapeutic target in cervical cancer.