Triple-negative breast cancer (TNBC) is the most aggressive subtype of
breast cancer and lacks approved specific targeted
therapies. One of the major reasons why TNBC is difficult to treat is the high proportion of cancer stem cells within the
tumor tissue. Nucleolus is the location of ribosome biogenesis which is frequently overactivated in
cancer cells and overactivation of ribosome biogenesis frequently drives the malignant transformation of
cancer. Nucleolar and coiled-body
phosphoprotein 1 (NOLC1) is a
nucleolar protein responsible for nucleolus organization and rRNA synthesis and plays an important role in ribosome biogenesis. However, the correlation of NOLC1 expression with patient prognosis and its value as a therapeutic target have not been evaluated in TNBC. In the current study, based on bioinformatics analysis of the online databases, we found that the expression of NOLC1 was higher in
breast cancer tissues than normal tissues, and NOLC1 was expressed at a higher level in TNBC than other subtypes of
breast cancer. GSEA analysis revealed that stemness-related pathways were significantly enriched in
breast cancer with high NOLC1 gene expression. Further analyses using gene expression profiling interactive analysis 2 (GEPIA2),
tumor immune estimation resource (TIMER) and search tool for retrieval of interacting genes/
proteins (STRING) demonstrated that NOLC1 was significantly associated with stemness in both all
breast cancer and basal-like
breast cancer/TNBC patients at both gene and
protein levels. Knockdown of NOLC1 by
siRNA decreased the
protein level of the key stemness regulators MYC and ALDH and inhibited the sphere-forming capacity in TNBC cell line MDA-MB-231. Univariate and multivariate Cox regression analyses demonstrated that NOLC1 was an independent risk factor for overall survival in
breast cancer. PrognoScan and Kaplan-Meier plotter analyses revealed that high expression of NOLC1 was associated with poor prognosis in both all
breast cancer and TNBC patients. Further immunohistochemical analysis of
breast cancer patient samples revealed that TNBC cells had a lower level of NOLC1 in the nucleus compared with non-TNBC cells. These findings suggest that NOLC1 is closely associated with the stemness properties of TNBC and represents a potential therapeutic target for TNBC.