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Updated: Sep 11, 2026

Genome-wide Screen for miRNA Targets Using the MISSION Target ID Library
Published on: April 6, 2012
MicroRNA-322 Promotes Granulosa Cell Senescence and Premature Ovarian Failure by Suppressing Klotho expression and
Zeyu Cui1, Yanchen Lai2, Xiangfeng Chen3
1Shanghai Geriatric Institute of Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 200031, China; Shanghai Key Laboratory of Molecular Imaging, Shanghai University of Medicine and Health Sciences, Shanghai, 201318, China.
Abstract:
Premature ovarian failure (POF) is closely linked to ovarian granulosa cell (OGC) senescence and cell cycle arrest. This study explored the role of the miR-322/Klotho axis in OGC aging. Using a cyclophosphamide-induced mouse model and cultured OGCs, we found Klotho significantly downregulated in POF, inversely correlating with elevated miR-322 and senescence markers p16, p21, and p53. Luciferase assays confirmed Klotho as a direct miR-322 target. miR-322 overexpression induced G0/G1 and G2/M phase arrest and OGC senescence by silencing Klotho, while miR-322 inhibition partially rescued the POF phenotype. miR-322 knock-in mice exhibited reduced ovarian weight, increased follicular atresia, and altered E2/FSH levels, mimicking clinical POF. Mechanistically, the miR-322/Klotho axis modulated cell cycle regulators, upregulating CHK1 and downregulating CDC25A, CDK2, and Cyclin A/E. Thus, miR-322 promotes OGC senescence and POF by targeting Klotho to activate cell cycle inhibition pathways, identifying this axis as a critical epigenetic regulator of ovarian aging and a potential therapeutic target.
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