OncoTargets and Therapy (Dec 2019)
miR-139 Controls Viability Of Ovarian Cancer Cells Through Apoptosis Induction And Exosome Shedding Inhibition By Targeting ATP7A
Abstract
Fang Xiao, Songshu Xiao, Min Xue Department of Obstetrics and Gynecology, Third Xiangya Hospital of Central South University, Changsha, Hunan 410013, People’s Republic of ChinaCorrespondence: Min XueDepartment of Obstetrics and Gynecology, Third Xiangya Hospital of Central South University, No. 138, Tongzipo Road, Yuelu District, Hexi, Changsha, Hunan 410013, People’s Republic of ChinaTel +86-13687354678Email [email protected]: Emerging proof suggests that microRNA (miRNA) malfunction is correlated to the generation and development of multiple malignancies. It has been proven that miRNA (miR)-139 represses a variety of malignancies. However, the understanding of its impact on ovarian cancer (OC) is insufficient. We aimed to investigate the expression and function of miR-139 in OC.Methods: The expression of mir-139 was detected and recorded, and the relationship of mir-139 remaining OC cells was explored. At the same time, we studied the correlation between ATP7A and mir-139 by the luciferase reporter test, Western blot, and quantitative real-time reverse transcription PCR.Results: The expression of miR-139 was remarkably downregulated in OC specimens. Furthermore, excessive miR-139 expression noticeably inhibited the migration, colony generation, proliferation, and invasion of OC cells. In addition, excessive miR-139 expression remarkably repressed the death and the expression of proteins related to cell death in OC cells, as well as inhibited the shedding of exosomes. According to the luciferase reporter test, Western blot, and quantitative real-time reverse transcription PCR, miR-139 directly targeted ATP7A. Furthermore, the expression of ATP7A was found to be negatively related to miR-139 levels in OC specimens. It was revealed via a rescue experiment that excessive ATP7A expression counteracted the repressive effect of miR-139 in OC cells.Conclusion: It was revealed via an in vivo study that miR-139 remarkably inhibited the growth of malignancies by downregulating ATP7A in nude mice. miR-139 represses the development of malignancies in OC by directly targeting ATP7A, offering an innovative approach for molecular therapy of OC.Keywords: apoptosis, ATP7A, exosome shedding, miR-139, ovarian cancer
