The impact of hsa-miR-1972 on the expression of von Willebrand factor in breast cancer progression regulation.

Abstract

Breast cancer (BC) is one of most frequent female malignancies that poses multiple challenges in treatment and prevention. This study aimed to explore the role of miRNAs and their target genes during the BC progression. Based on the BC data (113 normal and 1,118 tumor samples) from the TCGA-BRCA dataset, a single-sample gene set enrichment analysis (ssGSEA) was applied to calculate the cancer migration scores, and weighted gene co-expression network analysis (WGCNA) were performed using the WGCNA R package, with a focus on the set of genes associated with cancer migration. Key modules and hub genes related to cell migration and signaling pathways were identified. Survival analysis of hub genes was conducted using the survminer R package, and prediction of regulatory miRNAs were performed to analyze their impact on BC prognosis. In addition, the BC cell lines MCF-7 and MDA-MB-231 were used to further explore the effect of hsa-miR-1972 mimics on the gene expression and angiogenic factor regulation. The study classified important modules (MEblue, MEmagenta, MEpink, and MEfloralwhite) associated with cell migration and identified three hub genes, namely, MRPL20, COL4A1 and VWF. Survival analysis showed that certain hub genes with a low expression were related to a poor prognosis, whereas low-expressed COL4A1 and VWF were related to better survival outcomes. We also found that hsa-miR-1972 mimics significantly downregulated critical genes involved in BC metastasis and angiogenesis and effectively inhibited the proliferation of BC cell lines, showing a strong therapeutic potential. Manipulation of VWF expression in cells overexpressing hsa-miR-1972 had significant effects on the malignant markers and angiogenic factors, suggesting a novel therapeutic direction for BC treatment. Our study highlighted the complex interplay of genetic factors in BC progression as well as the therapeutic potential of targeting specific miRNAs and their related hub genes. These findings provided novel insights into the pathogenesis of BC and suggested new direction for the therapeutic development for the cancer.