MiR-509-5p downregulation is associated with male infertility and acts as a suppressor in testicular germ cell tumor cells through targeting MDM2

Abstract

Background: 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.