The pseudouridine synthase PUS7 is associated with stemness and represents a potential therapeutic target in triple-negative breast cancer cells.

Triple-negative breast cancer (TNBC) represents a highly aggressive subtype of breast cancer characterized by increased recurrence rates and poor prognosis, primarily due to the lack of effective therapeutic targets. Pseudouridine synthases (PUSs) are a class of enzymes that are responsible for catalyzing the isomerization of uridine to pseudouridine in RNA, thereby contributing to cancer progression. In the present study, we examined the roles of PUSs in modulating the biological properties of TNBC using bioinformatics and experimental investigations. Increased gene expression levels of PUSs, particularly PUS7, were identified in TNBC tissues from the TCGA RNA-seq dataset and were found to be associated with unfavorable survival of TNBC patients. In addition, increased protein levels of PUS7 were identified in TNBC patient tissues and cell lines compared with non-TNBC. The increased PUS7 expression was in line with the stemness of TNBC cells. Knockdown of PUS7 in MDA-MB-231 and MDA-MB-468 cells inhibited stemness, migration, and colony formation. Transfection with a PUS7-Mut construct, which eliminated the enzymatic activity of PUS7, reversed the stimulating effects of PUS7 on stemness, migration, and colony formation in TNBC cells. This study highlights the influence of PUS7 on the biological properties of TNBC through its enzymatic activity, providing valuable insights and potential avenues for the identification of effective therapeutic targets for TNBC.