miR-638 Inhibits immature Sertoli cell growth by indirectly inactivating PI3K/AKT pathway via SPAG1 gene
miR-638 Inhibits immature Sertoli cell growth by indirectly inactivating PI3K/AKT pathway via SPAG1 gene
复制标题
miR-638 通过 SPAG1 基因间接灭活 PI3K/AKT 通路，抑制未成熟支持细胞生长
DOI：
10.1080/15384101.2017.1380130
复制
发表时间：
2017-01-01
期刊：
影响因子：
4.3
通讯作者：
Li, Fenge
中科院分区：
文献类型：
--
作者：
Hu, Pandi;Guan, Kaifeng;Li, Fenge
大量研究表明microRNAs（miRNAs）在细胞生长、凋亡和精子发生中起重要作用。我们前期的研究表明miR-638在性未成熟和成熟的大白色公猪睾丸中存在差异表达。本文报道了精子相关抗原1（SPAG 1）是miR-638的直接靶基因。此外，miR-638还能抑制猪未成熟支持细胞的增殖和细胞周期，促进细胞凋亡。过表达miR-638或RNAi SPAG 1后，PI 3 K/AKT通路中的关键基因磷酸化磷脂酰肌醇3激酶（p-PI 3 K）和磷酸化丝氨酸/苏氨酸激酶（p-AKT）以及细胞周期因子c-MYC、细胞周期蛋白D1（CCND 1）、细胞周期蛋白E1（CCNE 1）和细胞周期蛋白依赖性激酶4（CDK 4）均显著下调。值得注意的是，SRY相关的HMG盒2（SOX 2）和POU结构域，5类转录因子1（POU 5 F1）的mRNA水平显着抑制精原细胞增殖在SPAG 1 siRNA转染ST细胞。本研究提示miR-638通过靶向SPAG 1基因调控未成熟支持细胞的生长和凋亡，间接阻断PI 3 K/AKT通路，在猪精子发生中发挥作用。
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.