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

**Authors:** Nour H. Elbazzar, Inas Moaz, Abeer A. Bahnassy, Ahmed El sherif, Ola S. Ahmed

PMC · DOI: 10.1038/s41598-025-13402-8 · Scientific Reports · 2025-08-08

## TL;DR

This study investigates the role of specific genes and non-coding RNAs in metastatic breast cancer, focusing on their potential as biomarkers for disease progression.

## Contribution

The study identifies SNAIL and FOXC2 as potential prognostic biomarkers for metastatic breast cancer stem cells.

## Key findings

- SNAIL and FOXC2 were significantly upregulated in metastatic breast cancer patients compared to healthy controls.
- FOXC2 and SNAIL showed a strong positive correlation, suggesting a shared role in disease progression.
- HOTAIR, UCA1, MALAT1, and ZEB did not show significant differences in expression between cancer and control groups.

## 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.

## Linked entities

- **Genes:** HOTAIR (HOX transcript antisense RNA) [NCBI Gene 100124700], UCA1 (urothelial cancer associated 1) [NCBI Gene 652995], MALAT1 (metastasis associated lung adenocarcinoma transcript 1) [NCBI Gene 378938], FOXC2 (forkhead box C2) [NCBI Gene 2303], SNAI1 (snail family transcriptional repressor 1) [NCBI Gene 6615], Zeb1 (zinc finger E-box binding homeobox 1) [NCBI Gene 21417]
- **Diseases:** breast cancer (MONDO:0004989)

## Full-text entities

- **Genes:** UCA1 (urothelial cancer associated 1) [NCBI Gene 652995] {aka CUDR, LINC00178, NCRNA00178, UCAT1, onco-lncRNA-36}, LONP1 (lon peptidase 1, mitochondrial) [NCBI Gene 9361] {aka CODASS, LON, LONP, LonHS, PIM1, PRSS15}, MALAT1 (metastasis associated lung adenocarcinoma transcript 1) [NCBI Gene 378938] {aka HCN, LINC00047, NCRNA00047, NEAT2, PRO2853, miPEP-52}, HOTAIR (HOX transcript antisense RNA) [NCBI Gene 100124700] {aka HOXAS, HOXC-AS4, HOXC11-AS1, NCRNA00072}, FOXC2 (forkhead box C2) [NCBI Gene 2303] {aka FKHL14, LD, MFH-1, MFH1}
- **Diseases:** Metastatic (MESH:D000092182), BC (MESH:D001943), Cancer (MESH:D009369), metastasis (MESH:D009362)
- **Species:** Homo sapiens (human, species) [taxon 9606]

## Full text

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## Figures

5 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12334764/full.md

## References

11 references — full list in the complete paper: https://tomesphere.com/paper/PMC12334764/full.md

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Source: https://tomesphere.com/paper/PMC12334764