Kinesin family member 4 a drives Cancer stem cell characteristics in breast Cancer: Insights from scRNA-Seq and experimental validation

Abstract

This study identifies cancer stem cell marker genes in breast cancer through an integrated analysis of single cell RNA sequencing and bulk RNA sequencing data. The breast cancer-related single-cell RNA sequencing dataset GSE180286 was analyzed to identify cancer stem cells populations and their marker genes, which were further validated using data from The Cancer Genome Atlas breast cancer dataset. Weighted gene co-expression network analysis revealed seven co-expression modules, with the Turquoise module showing a strong association with messenger RNA stemness indices. Venn diagram analysis identified 19 cancer stem cell marker genes, among which cyclin B1, cell division cycle associated 8, and kinesin family member 4 A were highlighted as core genes. Both in vitro and in vivo experiments demonstrated that silencing kinesin family member 4 A in breast cancer cell lines significantly reduced tumor sphere formation, proliferation, migration, and invasion. Additionally, the downregulation of kinesin family member 4 A in a nude mouse model markedly suppressed tumor growth. These findings suggest that cyclin B1, cell division cycle associated 8, and particularly kinesin family member 4 A are critical regulators of cancer stem cell properties in breast cancer and represent promising therapeutic targets.

Keywords: CCNB1; CDCA8; Cancer stem cell; Kinesin family member 4 a; LASSO regression; Nude mouse xenograft model; Single cell RNA sequencing; mRNA stemness indices.