OncoTargets and Therapy (Dec 2019)
miR-509-5p Downregulation Is Associated With Male Infertility And Acts As A Suppressor In Testicular Germ Cell Tumor Cells Through Targeting MDM2
Abstract
Jinxia Sun,1 Lei Niu,2 Shanxia Gao,1 Xijuan Yi,1 Jianxia Chen1 1Department of Reproductive Medicine, Linyi Central Hospital, Linyi City, Shandong Province 276400, People’s Republic of China; 2Department of Respiratory Medicine, Linyi Central Hospital, Linyi City, Shandong Province 276400, People’s Republic of ChinaCorrespondence: Jianxia ChenDepartment of Reproductive Medicine, Linyi Central Hospital, No. 17 Health Road, Yishui County, Linyi City, Shandong Province 276400, People’s Republic of ChinaTel +86-539-2264353Email [email protected]: The dysregulation of microRNAs (miRNAs) has been linked with male infertility. miR-509-5p is highly expressed in testis and exerts suppressive effects on multiple types of human cancers.Objectives: Yet, whether miR-509-5p is connected with male infertility and plays a role in testicular germ cell tumor (TGCT) have not been explored.Materials and methods: This study detected miR-509-5p expression in germ cells from MA patients, and further characterize its functional roles in the proliferation and apoptosis of TGCT cells in vitro.Results: We report that miR-509-5p is downregulated in germ cells from infertile men with maturation arrest (MA), which implies an inverse association between miR-509-5p level and male infertility. In addition, miR-509-5p suppresses proliferation and induces apoptosis of TGCT cells in vitro, suggesting that it exhibits tumor-suppressive effects on TGCT. Mechanistically, miR-509-5p targets the mouse double minute 2 (MDM2), an oncogenic factor in TGCT, and moreover, restored expression of MDM2 rescues miR-509-5p suppressive effects on TGCT cells, demonstrating that miR-509-5p suppresses TGCT cells through targeting MDM2.Conclusion: Collectively, these results implicate that miR-509-5p may participate in the pathogenesis of male infertility and TGCT through regulating proliferation and apoptosis, two critical cellular activities for spermatogenesis and TGCT tumorigenesis.Keywords: male infertility, testicular germ cell tumor, miR-509-5p, proliferation, apoptosis, MDM2
