Expression of SnoRNA U50A Is Associated with Better Prognosis and Prolonged Mitosis in Breast Cancer

SIMPLE SUMMARY: SnoRNAs are essential for fundamental cellular processes. However, emerging evidence shows that snoRNAs play regulatory roles during cancer progression. The snoRNA U50A (U50A) is a newly-identified putative tumor suppressor, but its clinical and mechanistic impacts in breast cancer remain elusive. In this study, we quantified the copy number of U50A in breast cancer patient tissues and found that a higher level of U50A expression is correlated with better overall survival in breast cancer patients. By utilizing transcriptomic analysis, we demonstrated that U50A prolongs mitosis and reduces colony-forming ability through downregulating mitosis-related genes. Consistent with these in vitro results, breast cancer tissues expressing higher U50A significantly exhibited accumulated mitotic tumor cells and were associated with reduced tumor size. Altogether, this is the first study showing the clinical, cellular, and regulatory impacts of snoRNA U50A in human breast cancer. ABSTRACT: Small nucleolar RNAs (snoRNAs) are small noncoding RNAs generally recognized as housekeeping genes. Genomic analysis has shown that snoRNA U50A (U50A) is a candidate tumor suppressor gene deleted in less than 10% of breast cancer patients. To date, the pathological roles of U50A in cancer, including its clinical significance and its regulatory impact at the molecular level, are not well-defined. Here, we quantified the copy number of U50A in human breast cancer tissues. Our results showed that the U50A expression level is correlated with better prognosis in breast cancer patients. Utilizing RNA-sequencing for transcriptomic analysis, we revealed that U50A downregulates mitosis-related genes leading to arrested cancer cell mitosis and suppressed colony-forming ability. Moreover, in support of the impacts of U50A in prolonging mitosis and inhibiting clonogenic activity, breast cancer tissues with higher U50A expression exhibit accumulated mitotic tumor cells. In conclusion, based on the evidence from U50A-downregulated mitosis-related genes, prolonged mitosis, repressed colony-forming ability, and clinical analyses, we demonstrated molecular insights into the pathological impact of snoRNA U50A in human breast cancer.