Breast cancer stem cells (BCSCs) are key players in carcinogenesis and development. Small nucleolar RNAs (snoRNAs) seem to have a crucial influence on regulating stem cell‐like properties in various cancers, but the underlying mechanism in breast cancer has not been determined. In this study, we first found that the expression of SNORA51 might be strongly and positively related to BCSCs‐like properties. SNORA51 expression was assessed in breast cancer tissues (n = 158 patients) by in situ hybridization. Colony formation, cell counting kit‐8, and sphere formation assays were used to detect cell proliferation and self‐renewal, respectively. Wound healing and transwell assays were used to detect cell migration. Coimmunoprecipitation and molecular docking were used to determine the underlying mechanism through which SNORA51 regulates BCSCs‐like properties. High SNORA51 expression was associated with a worse prognosis, overall survival, and disease‐free survival, in 158 breast cancer patients and was also closely related to lymph node status, ER status, the Ki‐67 index, histological grade, and TNM stage. Further analysis proved that SNORA51 could enhance and maintain stem cell‐like properties, including cell proliferation, self‐renewal, and migration, in breast cancer. Moreover, high SNORA51 expression could reduce nucleolar RPL3 expression, induce changes in the expression of NPM1 in the nucleolus and nucleoplasm, and ultimately increase c‐MYC expression. Taken together, our findings demonstrated that SNORA51 could enhance BCSCs‐like properties via the RPL3/NPM1/c‐MYC pathway both in vitro and in vivo. Therefore, SNORA51 might be a significant biomarker and potential therapeutic target and might even provide a new viewpoint on the regulatory mechanism of snoRNAs in breast cancer or other malignant tumors.

中文翻译：

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小核仁 RNA SNORA51 通过 RPL3/NPM1/c-MYC 通路增强乳腺癌干细胞样特性

乳腺癌干细胞（BCSC）是癌症发生和发展的关键参与者。小核仁 RNA (snoRNA) 似乎对调节各种癌症中的干细胞样特性具有至关重要的影响，但乳腺癌中的潜在机制尚未确定。在这项研究中，我们首先发现 SNORA51 的表达可能与 BCSC 样特性密切相关。在乳腺癌组织中评估了 SNORA51 的表达（n= 158 名患者）通过原位杂交。集落形成、细胞计数试剂盒-8和球体形成测定分别用于检测细胞增殖和自我更新。使用伤口愈合和transwell测定来检测细胞迁移。使用免疫共沉淀和分子对接来确定 SNORA51 调节 BCSC 样特性的潜在机制。在 158 名乳腺癌患者中，SNORA51 高表达与较差的预后、总生存期和无病生存期相关，并且还与淋巴结状态、ER 状态、Ki-67 指数、组织学分级和 TNM 分期密切相关。进一步的分析证明，SNORA51可以增强和维持乳腺癌中的干细胞样特性，包括细胞增殖、自我更新和迁移。此外，高SNORA51表达可以降低核仁RPL3表达，诱导核仁和核质中NPM1表达的变化，最终增加c-MYC表达。总而言之，我们的研究结果表明，SNORA51 可以在体外和体内通过 RPL3/NPM1/c-MYC 途径增强 BCSC 样特性。因此，SNORA51可能是一个重要的生物标志物和潜在的治疗靶点，甚至可能为snoRNA在乳腺癌或其他恶性肿瘤中的调控机制提供新的观点。