Plasticity, a key hallmark of cancer, enables cells to transition into different states, driving tumor heterogeneity. This cellular plasticity is associated with cancer progression, treatment resistance, and relapse. Cancer stem cells (CSCs) play a central role in this process, yet the molecular factors underlying cancer cell stemness remain poorly understood. In this study, we explored the role of XIST (X-inactive specific transcript) long noncoding RNA in ovarian cancer stemness and plasticity through in silico and in vitro analyses. We found that XIST is significantly down-regulated in ovarian tumors, with low XIST expression linked to a higher stemness index and lower overall survival. Knocking down XIST in ovarian cancer cells enhanced stemness, particularly increasing mesenchymal-like CSCs, and under hypoxic conditions, it promoted epithelial-like CSC markers. Our findings suggest that XIST loss leads to CSC enrichment and cellular plasticity in ovarian cancer, pointing to potential therapeutic targets for patients with low XIST expression.

中文翻译：

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XIST lncRNA 的缺失解锁卵巢癌的干性和细胞可塑性


可塑性是癌症的一个关键标志，它使细胞能够转变为不同的状态，从而驱动肿瘤异质性。这种细胞可塑性与癌症进展、治疗耐药性和复发有关。癌症干细胞 （CSCs） 在此过程中起着核心作用，但对癌细胞干性的分子因素仍然知之甚少。在这项研究中，我们通过计算机和体外分析探讨了 XIST （X 失活特异性转录物） 长链非编码 RNA 在卵巢癌干性和可塑性中的作用。我们发现 XIST 在卵巢肿瘤中显着下调，低 XIST 表达与较高的干性指数和较低的总生存期有关。敲除卵巢癌细胞中的 XIST 增强了干性，特别是增加了间充质样 CSCs，并且在缺氧条件下，它促进了上皮样 CSC 标志物。我们的研究结果表明，XIST 丢失导致卵巢癌中的 CSC 富集和细胞可塑性，为 XIST 表达低的患者提供了潜在的治疗靶点。