Long Noncoding RNA NONHSAT233728.1 Promotes ROS Accumulation and Granulosa Cell Apoptosis by Regulating the MAPK/ERK1/2 Signaling Pathway

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. Through isolation and transcriptomic profiling of granulosa cells, we identified the functional significance of lncRNA NONHSAT233728.1 in polycystic ovary syndrome (PCOS) pathogenesis. Knockdown of lncRNA NONHSAT233728.1 in granulosa cells elevated ROS levels, reduced the Bcl2/Bax ratio, downregulated phospho‐ERK1/2, and increased IL‐8 secretion. These results demonstrate ROS‐mediated mitochondrial apoptosis via MEK/ERK1/2 suppression, alongside inhibited proliferation and enhanced inflammation, consistent with follicular atresia in PCOS. Negative correlations between NONHSAT233728.1 and LH/FSH ratios further support its pathogenic role.