FASEB journal : official publication of the Federation of American Societies for Experimental Biology [FASEB J] 2025 Jun 15; Vol. 39 (11), pp. e70681.

Publisher: Federation of American Societies for Experimental Biology Country of Publication: United States NLM ID: 8804484 Publication Model: Print Cited Medium: Internet ISSN: 1530-6860 (Electronic) Linking ISSN: 08926638 NLM ISO Abbreviation: FASEB J Subsets: MEDLINE

Publication: 2020- : [Bethesda, Md.] : Hoboken, NJ : Federation of American Societies for Experimental Biology ; Wiley
Original Publication: [Bethesda, Md.] : The Federation, [c1987-

RNA, Long Noncoding*/genetics , RNA, Long Noncoding*/metabolism , Granulosa Cells*/metabolism , Granulosa Cells*/pathology , Apoptosis* , Polycystic Ovary Syndrome*/metabolism , Polycystic Ovary Syndrome*/genetics , Polycystic Ovary Syndrome*/pathology , Reactive Oxygen Species*/metabolism , MAP Kinase Signaling System*, Humans ; Female ; Adult ; Mitochondria/metabolism ; Cell Proliferation

Polycystic ovary syndrome (PCOS) is one of the most prevalent endocrine disorders in women of reproductive age. However, the underlying molecular mechanism remains unclear. In this study, we employed RNA sequencing analysis to identify differentially expressed protein-coding genes and long noncoding RNA (lncRNA) expression profiles in granulosa cells from women with and without PCOS. It was established that the level of NONHSAT233728.1 was diminished in women with PCOS. The present study demonstrated the role of NONHSAT233728.1 in granulosa cells from patients with PCOS and further investigated the potential mechanism of NONHSAT233728.1 in the KGN cell line. Additionally, the knockdown of NONHSAT233728.1 has been observed to promote cell apoptosis, inhibit cell proliferation, promote mitochondrial dysfunction, and inflammation. Western blot analyses confirmed that phospho-extracellular regulated protein kinases (ERK)1/2 were decreased following lnc-NONHSAT233728.1 knockdown. Consequently, we propose that ROS accumulation activates the endogenous mitochondrial apoptosis pathway, leading to granulosa cell apoptosis via the MEK/ERK1/2 pathway, which contributes to follicular atresia. We observed a negative correlation between NONHSAT233728.1 and both LH levels and the LH/FSH ratio. These findings indicate that lncRNA NONHSAT233728.1 is linked to the pathogenesis of PCOS and offer new insights into its underlying mechanisms.
(© 2025 The Author(s). The FASEB Journal published by Wiley Periodicals LLC on behalf of Federation of American Societies for Experimental Biology.)