LncRNA PWRN2 promotes polycystic ovary syndrome progression via epigenetically reducing ATRX by recruiting LSD1

Long non-coding RNA has been shown to mediate the progression of polycystic ovary syndrome (PCOS). However, the role and mechanism of Prader-Willi region nonprotein coding RNA 2 (PWRN2) in PCOS progression remain unclear. In our study, Sprague-Dawley rat was injected with dehydroepiandrosterone to mimic PCOS rat models. HE staining was used to assess the number of benign granular cells, and serum insulin and hormone levels were detected by ELISA kit. The expression of PWRN2 was examined by qRT-PCR. Ovarian granulosa cells (GCs) proliferation and apoptosis were examined by CCK-8 assay and flow cytometry. The protein levels of apoptosis markers and Alpha thalassemia retardation syndrome X-linked (ATRX) were determined by western blot. The interaction between lysine-specific demethylase 1 (LSD1) and PWRN2 or ATRX was confirmed by RIP and ChIP assay. Our data showed that PWRN2 was upregulated and ATRX was downregulated in the ovarium tissues and serum of PCOS rat. PWRN2 knockdown promoted GCs proliferation and inhibited apoptosis. In the mechanism, PWRN2 inhibited ATRX transcription by binding with LSD1. In addition, downregulation of ATRX also eliminated the effect of sh-PWRN2 on GCs growth. In conclusion, our data suggested that PWRN2 might restrain GCs growth to promote PCOS progression, which was achieved by binding with LSD1 to inhibit ATRX transcription.