MicroRNA-16 Promotes Ovarian Granulosa Cell Proliferation and Suppresses Apoptosis Through Targeting PDCD4 in Polycystic Ovarian Syndrome

Cellular Physiology and Biochemistry

Xiafei  Fu¹ 

关键词: Mir-16;    Granulosa cells;    PDCD4;    Testosterone;    Polycystic ovary syndrome;   

DOI  :  10.1159/000491894

学科分类：分子生物学，细胞生物学和基因

来源: S Karger AG

【 摘 要 】

Background/Aims Several miRNAs have been reported to be involved in the pathogenesis of polycystic ovarian syndrome (PCOS). However, the biological roles of miR-16 and its molecular mechanisms in PCOS development remain to be elucidated. Methods qRT-PCR was performed to detect the expression levels of miR-16 and programmed cell death protein 4 (PDCD4). GCs proliferation, cell cycle distribution and apoptosis were examined by MTT assay and flow cytometry analysis. Luciferase reporter assay and RIP assay were applied to confirm the regulatory relationship between miR-16 and PDCD4. Western blot was applied to measure the protein levels of PDCD4, PCNA and caspase-3. ELISA kits were used to determine the serum levels of steroids. Results miR-16 expression was down-regulated in ovarian cortex tissues and serums of PCOS patients. PDCD4 expression was up-regulated in ovarian cortex tissues of PCOS patients. miR-16 overexpression facilitated cell proliferation, induced cell cycle progression, and inhibited apoptosis in GCs. Moreover, PDCD4 was a direct target of miR-16. Also, enforced expression of PDCD4 abated the effects of miR-16 on GCs growth and apoptosis. Additionally, testosterone resulted in a decrease of miR-16 expression and an increase of PDCD4 expression, thus blocking cell growth and enhanced apoptosis in GCs. Furthermore, miR-16 overexpression alleviated PCOS in vivo by regulating PDCD4. Conclusions miR-16 promoted ovarian GCs proliferation and inhibited apoptosis through directly targeting PDCD4 in PCOS, contributing to a better understanding of the molecular mechanism of GCs dysregulation and providing a promising target in PCOS.

【 授权许可】

CC BY-NC-ND