期刊
BIOCHIMICA ET BIOPHYSICA ACTA-GENE REGULATORY MECHANISMS
卷 1862, 期 10, 页码 -出版社
ELSEVIER
DOI: 10.1016/j.bbagrm.2019.194420
关键词
CTGF; miR-10a-5p; circINHA; Granulosa cell; Apoptosis; ceRNA
资金
- National Natural Science Foundation of China [31672421]
- Natural Science Foundation of Jiangsu Province [BK20161453, BK20160721]
- Fundamental Research Funds for the Central Universities [KYZ201644]
Mammalian ovarian follicular atresia is a complex and fine-regulated biological process with active involvement of connective tissue growth factor (CTGF). The emergence of studies of endogenous non-coding RNAs has raised a new aspect for exploration of the regulatory mechanisms involved in follicular atresia. Here, we aimed to illustrate a circRNA involved in the CTGF regulatory pathway during the apoptosis and follicular atresia of pig granulosa cells (GCs). We first detected a decreased expression pattern of CTGF during follicular atresia using IHC, FISH and qRT-PCR and confirmed the anti-apoptosis effect of CTGF in GCs in vitro by CTGF siRNA knockdown. Then, we used a dual luciferase activity assay to demonstrate CTGF as a direct functional target of miR-10a-5p, which was upregulated in atresic follicles and promoted the apoptosis of GCs in vitro. The negative effect of miR-10a-5p on GC viability was confirmed by cell cycle assays, cell proliferation/apoptosis assays and the WB detection of marker proteins. More importantly, we identified a novel circRNA, termed circINHA, that was downregulated during atresia in ovarian follicles, and we confirmed a direct interaction between miR-10a-5p and circINHA. Finally, we demonstrated that circINHA promoted GCs proliferation and inhibited GCs apoptosis via CTGF as a competing endogenous RNA (ceRNA) that directly bound to miR-10a-5p. Taken together, this study provides evidence for the circINHA/miR-10a-5p/CTGF regulatory pathway in follicular GC apoptosis and provides novel insights into the role of circRNAs in the modulation of ovarian physiological functions.
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