Abstract：
Polycystic ovary syndrome (PCOS) is a type of follicular dysplasia with an unclear pathogenesis, posing certain challenges in its diagnosis and treatment. Cancer susceptibility candidate 15 (CASC15), a long non-coding RNA closely associated with tumour development, has been implicated in PCOS onset and development. Therefore, this study aimed to investigate the molecular mechanisms underlying PCOS by downregulating CASC15 expression in both in vitro and in vivo models. We explored the potential regulatory relationship between CASC15 expression and PCOS by examining cell proliferation, cell cycle dynamics, cell autophagy, steroid hormone secretion capacity, and overall ovarian function in mice. We found that CASC15 expression in granulosa cells derived from patients with PCOS was significantly higher than those of the normal group (P < 0.001). In vitro experiments revealed that downregulating CASC15 significantly inhibited cell proliferation, promoted apoptosis, induced G1-phase cell cycle arrest, and influenced cellular autophagy levels. Moreover, downregulating CASC15 affected the follicular development process in newborn mouse ovaries. In vivo studies in mice demonstrated that disrupting CASC15 expression improved PCOS-related symptoms such as polycystic changes and hyperandrogenism, and significantly affected ovulation induction and embryo implantation in pregnant mice. Overall, CASC15 was highly expressed in granulosa cells of patients with PCOS and its downregulation improved PCOS-related symptoms by influencing granulosa cell function and follicular development in mice.
摘要：
多囊卵巢综合征（PCOS）是一种卵泡发育不良，发病机制尚不清楚，对其诊断和治疗提出了一定的挑战。癌症易感性候选者15（CASC15），与肿瘤发展密切相关的长链非编码RNA，与PCOS的发病和发展有关。因此,本研究旨在研究PCOS在体外和体内模型中下调CASC15表达的分子机制。我们通过检测细胞增殖，探索CASC15表达与PCOS之间的潜在调控关系。细胞周期动力学，细胞自噬，类固醇激素分泌能力，和小鼠的总体卵巢功能。我们发现PCOS患者颗粒细胞中CASC15的表达明显高于正常组（P<0.001）。体外实验表明下调CASC15显著抑制细胞增殖,促进细胞凋亡，诱导G1期细胞周期停滞，并影响细胞自噬水平。此外，下调CASC15影响新生小鼠卵巢的卵泡发育过程。小鼠体内研究表明，破坏CASC15表达可改善PCOS相关症状，如多囊变化和高雄激素血症。并显着影响妊娠小鼠的排卵诱导和胚胎植入。总的来说,CASC15在PCOS患者的颗粒细胞中高表达，其下调通过影响小鼠颗粒细胞功能和卵泡发育改善PCOS相关症状。
