miR-509-5p Downregulation Is Associated With Male Infertility And Acts As A Suppressor In Testicular Germ Cell Tumor Cells Through Targeting MDM2

• Main Authors: Sun J, Niu L, Gao S, Yi X, Chen J
• Format: Article
• Language: English
• Published: Dove Medical Press 2019-12-01
• Series: OncoTargets and Therapy
• Subjects: male infertility; testicular germ cell tumor; mir-509-5p; proliferation; apoptosis; mdm2
• Online Access: https://www.dovepress.com/mir-509-5p-downregulation-is-associated-with-male-infertility-and-acts-peer-reviewed-article-OTT

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 [phone]Email [e-mail]: 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