卵巢癌干细胞（OCSCs）是卵巢癌复发和耐药的根源。核糖体合成与应激平衡是干性维持的关键环节，RPL5/11是介导核糖体合成与应激平衡的关键因子。SNORNAs作为介导细胞核异质性的核心因子，是否介导核糖体合成与应激平衡影响OCSCs特性？课题组发现：SNORA72过表达升高核仁中RPL5/11表达、降低核质中表达；SNORA72诱导OCSCs核糖体合成增加的同时，应激途径减弱；同步检测到SNORA72与OCSCs密切相关的HIF-2α表达正相关。本项目拟在确认RPL5/11核内移位是OCSCs中SNORA72调控核糖体合成与应激平衡的关键环节基础上，明确SNORA72调控OCSCs干性的机制；确认HIF-2α与SNORA72关键HRE元件，阐明HIF-2α转录激活SNORA72进而调节OSCSs的核糖体合成与应激平衡的分子机制。本研究为揭示OCSCs干性形成新机制与新靶点提供依据。

Ovarian cancer stem cells (OCSCs) are responsible for the recurrence and chemoresistance of ovarian cancer. The balance between ribosomal synthesis process and ribosomal stress plays a key role in maintaining stemness of cancer cells, and RPL5/11 are key factors in mediating the balance between ribosomal synthesis process and ribosomal stress. Do SNORNAs, as core factors mediating nuclear heterogeneity, mediate the balance between ribosomal synthesis process and ribosomal stress and then affect the characteristics of OCSCs? What are the possible regulatory mechanisms? We found that the overexpression of SNORA72 increased RPL5/11 expression in nucleoli and decreased the expression of those in the nucleoplasm, and SNORA72 increased ribosomal synthesis process and depressed the ribosomal stress in OCSCs. HIF-2α, which is closely related to OCSCs, was detected simultaneously and was positively correlated with the expression of SNORA72. This project is to confirm the mechanism of regulating RPL5/11-MDM2-P53 ribosomal stress based on the identification of SNORA72 recruitment of RPL5/11 nucleolar translocation as a key step, and confirm the key HRE elements of HIF-2α binding to the host gene of SNORA72, and then clarify the molecular mechanism that SNORA72 is activated by HIF-2α, and then regulates the stemness of OCSCs by inhibiting ribosomal stress. This project will provide a new idea and target for deep researching the mechanism of maintaining the OCSCs characteristics.