The small nucleolar RNA SNORA51 enhances breast cancer stem cell-like properties via the RPL3/NPM1/c-MYC pathway.

Abstract

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.Coimmunoprecipitationand 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.