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  • Title: miR-638 Inhibits immature Sertoli cell growth by indirectly inactivating PI3K/AKT pathway via SPAG1 gene.
    Author: Hu P, Guan K, Feng Y, Ma C, Song H, Li Y, Xia X, Li J, Li F.
    Journal: Cell Cycle; 2017; 16(23):2290-2300. PubMed ID: 29119857.
    Abstract:
    Numerous studies have demonstrated that microRNAs (miRNAs) play important roles in cell growth, apoptosis and spermatogenesis. Our previous study showed that miR-638 was differentially expressed in sexually immature and mature testes of Large White boars. Here we reported that sperm-associated antigen 1 (SPAG1) was a direct target gene of miR-638. Moreover, miR-638 inhibited cell proliferation and cell cycle, and promoted apoptosis of porcine immature Sertoli cells. Key genes including phosphorylated phosphatidylinositide 3-kinases (p-PI3K) and phosphorylated serine/ threonine kinase (p-AKT) in PI3K/AKT pathway as well as cell cycle factors including c-MYC, cyclin-D1 (CCND1), cyclin-E1 (CCNE1) and cyclin-dependent kinase 4 (CDK4) were all significantly down-regulated after overexpression of miR-638 or RNAi of SPAG1. Notably, mRNA levels of SRY-related HMG-box 2 (SOX2) and POU domain, class 5, transcription factor 1 (POU5F1) essential for spermatogonia proliferation were significantly suppressed in SPAG1 siRNA- transfected ST cells. This study suggests that miR-638 regulates immature Sertoli cell growth and apoptosis by targeting SPAG1 gene which can indirectly inactivate PI3K/AKT pathway, and plays roles in pig spermatogenesis.
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