Cancer stem cells and Lon-noncRNA promotes invasion, metastasis and tumor growth in breast cancer through regulation of signaling pathway

Abstract

Breast cancer (BC), the most common malignant tumor in women, continues to be a leading cause of cancer-related deaths globally. A major challenge in managing BC, especially in metastatic cases, is the lack of reliable early diagnostic biomarkers. Metastatic breast cancer stem cells (MBCSCs) play a critical role in tumor progression, resistance to therapy, and disease recurrence. This study aimed to explore the molecular pathways connecting the long non-coding RNAs (lncRNAs) HOTAIR, UCA1, and MALAT1 with breast cancer stem cell-related genes FOXC2, SNAIL, and ZEB, focusing on their involvement in transcriptional regulation, proliferation, and survival. Peripheral blood samples and plasma were collected from 30 women diagnosed with metastatic breast cancer (MBC, stage IV) and 30 healthy controls. Gene expression levels were measured using quantitative real-time PCR (qRT-PCR). Our findings revealed a significant upregulation of SNAIL and FOXC2 in MBC patients compared to healthy controls (p < 0.001). The median expression levels of SNAIL (16.4) and FOXC2 (19.5) were substantially higher in the metastatic group than in healthy individuals (SNAIL: 6.42, FOXC2: 7.23). Conversely, the expression levels of HOTAIR, UCA1, MALAT1, and ZEB did not show statistically significant differences between the two groups (p > 0.05). Correlation analysis indicated a strong positive association between FOXC2 and SNAIL expression (r = 0.41), suggesting a potential shared functional role in disease progression. These results suggest that SNAIL and FOXC2 could serve as potential prognostic biomarkers in MBCSCs, whereas HOTAIR, UCA1, MALAT1, and ZEB may not independently predict metastasis or survival outcomes. Further research is necessary to explore the therapeutic implications of these genes in metastatic breast cancer.

Keywords: Breast cancers; Cancer stem cell; Long non coding RNA.

Fig. 1

Kaplan–Meier survival curve for comparison of overall survival (os) by hotair expression levels.

Fig. 2

Kaplan–Meier survival curve for overall survival by ZEB expression levels.

Fig. 3

Kaplan–Meier survival curve for comparison of overall survival (OS) by UCA1 expression levels.

Fig. 4

Kaplan–Meier survival curve for comparison of overall survival (OS) by MAIAT1 expression levels.

Fig. 5

Correlation heatmap of Gene expression levels: the heatmap visualizes the correlation coefficients between the expression levels of six genes: HOTAIR, UCA1, MALAT1, ZEB, Snail, and Fox. Positive correlations are represented by red shades, while negative correlations are shown in blue, with intensity reflecting the strength of the correlation.