Loss of XIST lncRNA unlocks stemness and cellular plasticity in ovarian cancer

• 成果类型: Article
• 署名作者: Naciri, Ikrame; Liang, Minzhi; Yang, Ying; Karner, Heather; Lin, Benjamin; Ludena, Maria De Lourdes Andrade; Hanse, Eric A.; Lebron, Alfredo; Razorenova, Olga, V; Nicholas, Dequina; Kong, Mei; Sun, Sha
• 署名单位: University of California System; University of California Irvine; University of California System; University of California Irvine; University of Notre Dame; University of Notre Dame; University of California System; University of California San Francisco; University of Alabama System; University of Alabama Birmingham; University of Alabama System; University of Alabama Birmingham
• 刊物名称: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
• ISSN/ISSBN: 0027-10864
• DOI: 10.1073/pnas.2418096121
• 发表日期: 2024-11-19
• 关键词: x-chromosome; dosage compensation; mesenchymal stem; cells; marker; rna; identification; hallmarks; hypoxia; met

摘要

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.