Long non-coding RNA lnc-CCNL1-3:1 promotes granulosa cell apoptosis and suppresses glucose uptake in women with polycystic ovary syndrome

• Main Authors: Jiayu Huang, Jun Zhao, Xueying Geng, Weiwei Chu, Shang Li, Zi-Jiang Chen, Yanzhi Du
• Format: Article
• Language: English
• Published: Elsevier 2021-03-01
• Series: Molecular Therapy: Nucleic Acids
• Subjects: LncRNA; Polycystic ovary syndrome; Granulosa cells; Follicular atresia; Insulin resistance
• Online Access: http://www.sciencedirect.com/science/article/pii/S2162253120303899

Polycystic ovary syndrome (PCOS) is a common endocrine and metabolic disease in premenopausal women. Long non-coding RNAs (lncRNAs) constitute important factors in numerous biological processes. However, their roles in PCOS pathogenesis require further clarification. Our study aims to elucidate the roles of lncRNA lnc-CCNL1-3:1 (CCNL) in PCOS. CCNL expression in human luteinized granulosa cells (hLGCs) derived from women with and without PCOS was detected. The full length of CCNL was obtained by 5′ and 3′ rapid amplification of cDNA ends. CCNL roles in granulosa cell apoptosis, mitochondrial function, and glucose uptake were evaluated. The binding relationship between CCNL and forkhead box O1 (FOXO1) was determined by RPISeq, RNA immunoprecipitation, subcellular fractionation, and immunofluorescence. In KGN cells and hLGCs, CCNL overexpression upregulated FOXO1 expression, promoted cell apoptosis, reduced glucose transport capability, and impaired mitochondrial function, and these effects were partially abolished by silencing FOXO1. The interaction of CCNL with FOXO1 might prevents FOXO1 exclusion from the nucleus and subsequent degradation in the cytosol. We determined that CCNL serve as a facilitator in the processes of PCOS. CCNL might participate in PCOS pathologies such as follicular atresia and insulin resistance.