POC1A promotes malignant phenotypes in non-triple-negative breast cancer cell models with EMT- and Wnt/β-catenin-related alterations

POC1A has been implicated in tumorigenesis in several malignancies; however, its expression pattern, clinical significance, and biological role in breast cancer remain unclear. This study aimed to investigate the expression of POC1A in breast cancer, evaluate its potential clinical relevance, and explore its role in tumor-associated phenotypes.

Differential expression of POC1A in breast cancer was analyzed using data from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases, and its associations with clinicopathological characteristics and patient prognosis were evaluated. Survival analysis was further performed using the Kaplan-Meier Plotter database. Univariate and multivariate Cox regression analyses were performed to assess the prognostic significance of POC1A, and gene set enrichment analysis was conducted to predict signaling pathways potentially associated with POC1A. Immunohistochemistry was subsequently performed to determine POC1A protein expression in breast cancer tissues and analyze its correlations with clinicopathological features and clinical outcomes. In addition, POC1A knockdown and overexpression models were established in MCF-7 and SK-BR-3 cells, representing luminal and HER2-positive non-triple-negative breast cancer cell models, respectively. Cell proliferation, cell-cycle distribution, migration, and invasion were assessed using CCK-8, colony formation, flow cytometry, and Transwell assays. Western blotting was performed to examine the expression of key molecules involved in the Wnt/β-catenin signaling pathway and epithelial-mesenchymal transition (EMT).

POC1A was significantly upregulated in breast cancer tissues in public datasets and showed potential discriminatory ability between breast cancer and normal breast tissues, with an area under the curve (AUC) of 0.879 in the TCGA cohort and 0.901 in the GSE22820 cohort. High POC1A expression was significantly associated with larger tumor size and advanced clinical stage. In the TCGA cohort, multivariate Cox regression analysis identified high POC1A expression as an independent risk factor for poor prognosis in patients with breast cancer based on the included covariates (HR = 1.049, 95% CI: 1.010-1.089, P = 0.014). Kaplan-Meier Plotter analysis further showed that high POC1A mRNA expression was significantly associated with poorer survival outcomes in patients with breast cancer. Immunohistochemical analysis further confirmed elevated POC1A protein expression in breast cancer tissues and its associations with tumor size and clinical stage. However, POC1A protein expression was not validated as an independent prognostic factor in the tissue microarray cohort. Functionally, POC1A knockdown suppressed breast cancer cell proliferation, colony formation, migration, and invasion, whereas POC1A overexpression exerted the opposite effects. At the molecular level, POC1A modulation was associated with changes in Wnt/β-catenin signaling-related proteins and EMT-related markers.

POC1A is overexpressed in breast cancer and may contribute to malignant phenotypes in non-triple-negative breast cancer cell models by promoting cell proliferation, migration, and invasion. These effects may be associated, at least in part, with alterations in Wnt/β-catenin signaling-related proteins and EMT-related markers. POC1A may represent a candidate molecular marker and potential target for further investigation in breast cancer, although its diagnostic, prognostic, and mechanistic significance requires further validation.