癌症干细胞和Lon-非编码RNA通过信号通路的调控促进乳腺癌的侵袭、转移和肿瘤生长。
Cancer stem cells and Lon-noncRNA promotes invasion, metastasis and tumor growth in breast cancer through regulation of signaling pathway.
作者信息
Elbazzar Nour H, Moaz Inas, Bahnassy Abeer A, El Sherif Ahmed, Ahmed Ola S
机构信息
Biotechnology Department, Faculty of Science, Cairo University, Giza, Egypt.
Epidemiology and Preventive Medicine at National Liver Institute, Shebeen El Kom, Egypt.
出版信息
Sci Rep. 2025 Aug 8;15(1):29021. doi: 10.1038/s41598-025-13402-8.
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.
乳腺癌(BC)是女性中最常见的恶性肿瘤,仍然是全球癌症相关死亡的主要原因。管理乳腺癌,尤其是转移性病例的一个主要挑战是缺乏可靠的早期诊断生物标志物。转移性乳腺癌干细胞(MBCSCs)在肿瘤进展、治疗抵抗和疾病复发中起关键作用。本研究旨在探索长链非编码RNA(lncRNAs)HOTAIR、UCA1和MALAT1与乳腺癌干细胞相关基因FOXC2、SNAIL和ZEB之间的分子途径,重点关注它们在转录调控、增殖和存活中的作用。从30名被诊断为转移性乳腺癌(MBC,IV期)的女性和30名健康对照中收集外周血样本和血浆。使用定量实时PCR(qRT-PCR)测量基因表达水平。我们的研究结果显示,与健康对照相比,MBC患者中SNAIL和FOXC2显著上调(p < 0.001)。转移性组中SNAIL(16.4)和FOXC2(19.5)的中位表达水平显著高于健康个体(SNAIL:6.42,FOXC2:7.23)。相反,两组之间HOTAIR、UCA1、MALAT1和ZEB的表达水平没有统计学显著差异(p > 0.05)。相关性分析表明FOXC2和SNAIL表达之间存在强正相关(r = 0.41),表明在疾病进展中可能具有潜在的共同功能作用。这些结果表明,SNAIL和FOXC2可作为MBCSCs中的潜在预后生物标志物,而HOTAIR、UCA1、MALAT1和ZEB可能无法独立预测转移或生存结果。有必要进一步研究这些基因在转移性乳腺癌中的治疗意义。