The regulatory role of cancer stem cell marker gene CXCR4 in the growth and metastasis of gastric cancer

Abstract

Single-cell RNA sequencing (scRNA-seq) and bulk RNA sequencing (bulk RNA-seq) are increasingly used for screening genes involved in carcinogenesis due to their capacity for dissecting cellular heterogeneity. This study aims to reveal the molecular mechanism of the cancer stem cells (CSCs) marker gene CXCR4 in gastric cancer (GC) growth and metastasis through scRNA-seq combined with bulk RNA-seq. GC-related scRNA-seq data were downloaded from the GEO database, followed by UMAP cluster analysis. Non-malignant cells were excluded by the K-means algorithm. Bulk RNA-seq data and clinical sample information were downloaded from the UCSC Xena database. GO and KEGG pathway analyses validated the correlation between genes and pathways. In vitro and in vivo functional assays were used to examine the effect of perturbed CXCR4 on malignant phenotypes, tumorigenesis, and liver metastasis. A large number of highly variable genes were identified in GC tissue samples. The top 20 principal components were selected, and the cells were clustered into 6 cell types. The C4 cell cluster from malignant epithelial cells might be CSCs. CXCR4 was singled out as a marker gene of CSCs. GC patients with high CXCR4 expression had poor survival. Knockdown of CXCR4 inhibited the malignant phenotypes of CSCs in vitro and curtailed tumorigenesis and liver metastasis in nude mice. CSC marker gene CXCR4 may be a key gene facilitating malignant phenotypes of CSCs, which thus promotes tumor growth and liver metastasis of GC.