Xu Xiaomeng, Yin Cheng, Dong Bing, Li Yuewen, Liu Shi, Chen Jun
Gynecology Department 2, The Third Affiliated Hospital of Qiqihar Medical University, No. 27 Taishun Street, Qiqihar, 161000, China.
Obstetrics Department, The Third Affiliated Hospital of Qiqihar Medical University, Qiqihar, 161000, China.
Biochem Genet. 2025 Apr;63(2):1686-1698. doi: 10.1007/s10528-024-10777-7. Epub 2024 Apr 12.
The polycystic ovary syndrome (PCOS), a common endocrine disorder, is mainly related to infertility. Moreover, it is characterized by promoted androgen, suppressed ovulation and insulin resistance. Long non-coding RNA X inactive specific transcript (lncRNA XIST), known as an oncogene or a cancer inhabited factor, is involved in several disease. However, the diagnostic mechanisms of lncRNA XIST in PCOS have not been clarified. Our study aimed to explain whether lncRNA XIST regulates KGN cells proliferation and apoptosis via microRNA (miR)-212-3p/RASA1 axis in PCOS. Levels of lncRNA XIST, miR-212-3p and RASA1 in KGN cells were detected through reverse transcription quantitative polymerase chain reaction (RT-qPCR) assay. Fluorescence in situ Hybridization (FISH) was performed to confirm the expression of lncRNA XIST and miR-212-3p in KGN cells. StarBase and dual-luciferase reporter assay were applied for exploring the interaction between miR-212-3p and RASA1. Cell viability, apoptosis, protein expression of Bcl-2 and Bax were assessed by MTT, flow cytometry analysis, RT-qPCR and western blot, respectively. We found that lncRNA XIST was low-expressed, miR-212-3p was over-expressed, and RASA1 was dramatically down-regulated in KGN cells. LncRNA XIST negatively regulated miR-212-3p expression in KGN cells. MiR-212-3p interacted with RASA1 and negatively regulated RASA1 levels in KGN cells. Up-regulation of lncRNA XIST signally decreased cells viability, stimulated more apoptotic cells, enhanced Bax expression, and depressed Bcl-2 level in KGN cells. However, these observations were abolished after miR-212-3p mimic treatment. Furthermore, miR-212-3p inhibitor significantly inhibited cell proliferation, enhanced more apoptotic cells, increased Bax expression, and decreased Bcl-2 level in KGN cells, and these effects were eliminated by RASA1-siRNA transfection. Our observations revealed that lncRNA XIST protects against PCOS through regulating miR-212-3p/RASA1 axis, suggesting that lncRNA XIST may be a promising therapeutic target for PCOS therapy.
多囊卵巢综合征（PCOS）是一种常见的内分泌紊乱疾病，主要与不孕有关。此外，其特征为雄激素升高、排卵受抑制和胰岛素抵抗。长链非编码RNA X失活特异性转录本（lncRNA XIST），被认为是一种癌基因或癌症抑制因子，参与多种疾病。然而，lncRNA XIST在PCOS中的诊断机制尚未阐明。我们的研究旨在解释lncRNA XIST是否通过微小RNA（miR）-212-3p/RASA1轴调节PCOS中KGN细胞的增殖和凋亡。通过逆转录定量聚合酶链反应（RT-qPCR）检测KGN细胞中lncRNA XIST、miR-212-3p和RASA1的水平。进行荧光原位杂交（FISH）以确认lncRNA XIST和miR-212-3p在KGN细胞中的表达。应用StarBase和双荧光素酶报告基因检测来探索miR-212-3p与RASA1之间的相互作用。分别通过MTT、流式细胞术分析、RT-qPCR和蛋白质印迹法评估细胞活力、凋亡、Bcl-2和Bax的蛋白质表达。我们发现lncRNA XIST在KGN细胞中低表达，miR-212-3p过表达，RASA1显著下调。lncRNA XIST在KGN细胞中负向调节miR-212-3p的表达。miR-212-3p与RASA1相互作用并负向调节KGN细胞中RASA1的水平。lncRNA XIST的上调显著降低细胞活力，刺激更多凋亡细胞，增强Bax表达，并降低KGN细胞中Bcl-2水平。然而，在miR-212-3p模拟物处理后，这些观察结果被消除。此外，miR-212-3p抑制剂显著抑制KGN细胞增殖，增强更多凋亡细胞，增加Bax表达，并降低Bcl-2水平，并且这些作用通过RASA1-siRNA转染被消除。我们的观察结果表明，lncRNA XIST通过调节miR-212-3p/RASA1轴预防PCOS，提示lncRNA XIST可能是PCOS治疗的一个有前景的治疗靶点。
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