MiRNA-708 Regulates Cell Growth And Cisplatin Sensitivity By Targeting Timeless In Cervical Cancer

Purpose: Cervical cancer is the fourth most common cause of cancer-associated mortality in women worldwide.Previous studies have reported that micro RNAs(mi RNAs)are involved in multiple biological aspects of cancer progression by regulating gene expression.Here,we investigated the role of mi R-708 in cervical cancer.Methods: The expression levels of mi R-708 in cervical cancer tissues and paired adjacent tissues were tested by real-time q PCR.The interaction between mi R-708 and Timeless was identified by bioinformatics,luciferase reporter gene assays and western blotting.The effect of mi R-708 overexpression on cell growth and cisplatin sensitivity were determined by CCK-8 and colony formation assay.Cell cycle and apoptosis were analyzed by flow cytometry.DNA damage induced by mi R-708 overexpression was determined by comet assay.The protein levels of the genes involved in DNA damage repair pathway were analyzed by western blotting.Results: The expression levels of mi R-708 were significantly down-regulated in cervical cancer tissues compared with paired adjacent tissues.By bioinformatics,western blotting analyses and dual luciferase reporter assays,we found Timeless is a direct target of mi R-708.Furthermore,the overexpression of mi R-708 could suppress proliferation,colonic growth,promoted apoptosis and upregulate DNA damage levels.Besides,we revealed that overexpression of mi R-708 facilitated cisplatin sensitivity in cervical cancer cells via impairing the ATR/CHK1 signal pathway,which was involved in DNA damage repair process.Conclusions: The overexpression of mi R-708 in cervical cancer cells suppresses proliferation and facilitates cisplatin sensitivity by impairing DNA repair pathway.The results of the present study demonstrated that mi R-708 might be a candidate therapeutic target for future cervical cancer therapy.