PNO1 served as a potential biomarker to promote the stemness and progression of breast cancer via the NF-κB signaling pathway

Abstract Background Breast cancer is a highly heterogeneous disease with diverse phenotypes. At present, increasing evidence supports the role of ribosomal biogenesis in human diseases and tumorigenesis. PNO1, as a ribosome assembly factor, plays a key role in the biological synthesis of ribosomes and ribosomal protein mutations associated with human diseases and tumor development. This study explored PNO1's role as a prognostic biomarker for breast cancer. Methods Clinical samples and online datasets were used to determine PNO1 expression in breast cancers with different molecular phenotypes and clinicopathological subtypes. CCK-8 assays, colony formation assays, wound healing, and transwell assays were performed to investigate tumor cell proliferation, migration, and invasion. Western blot, flow cytometry, and sphere-formation assays were used to assess the effect of PNO1 on breast cancer stemness. RNA-sequencing analysis was also performed to elucidate the underlying mechanism. Results Results showed that the expression level of PNO1 was upregulated in breast cancer samples. In addition, high PNO1 expression was positively correlated with poor survival in breast cancer patients with different molecular types. Moreover, PNO1 was associated with breast cancer heterogeneity by promoting its stem-like properties both in vitro and in vivo through the NF-κB signaling pathway, which can be suppressed by JSH-23. Conclusions Our study found that PNO1 expression was positively correlated with poor survival in different molecular subtypes of breast cancer and that PNO1 promoted stem-like properties of breast cancer by activating NF-κB activity. Collectively, PNO1 is a potential prognostic biomarker that plays an important role in breast cancer progression.