Abstract

Simple SummaryTriple-negative breast cancer (TNBC) is a type of breast cancer characterized by a lack of hormone receptors expression and HER2 gene amplification, which presents with a high probability of metastasis. Bone marrow mesenchymal stem cell-derived exosomes have an influence in the development of various tumors. This study set out to analyze the interaction of the ALKBH5/UBE2C/p53 axis and the molecular mechanism mediated by BMSC-Exos in the stemness property of TNBC cells based on the data of The Cancer Genome Atlas and Gene Expression Omnibus as well as in vivo animal experiments. which renders varieties of potential molecular targets in cancer therapy of TNBC.AbstractBackground: Abnormal N6-methyladenosine (m6A) modification caused by m6A regulators is a common characteristic in various tumors. However, little is known about the role of m6A regulator AlkB homolog 5 (ALKBH5) in triple-negative breast cancer (TNBC). In this study, we analyzed the influence of ALKBH5 on the stemness of TNBC and the molecular mechanism using bioinformatics analysis and in vivo animal experiments. Methods: RNA expression data and single-cell RNA sequencing (scRNA-seq) data were downloaded from the TCGA and GEO databases. Following intersection analysis, key genes involved in the TNBC cell stemness were determined, which was followed by functional enrichment analysis, PPI and survival analysis. Exosomes were extracted from bone marrow mesenchymal stem cells (BMSC-Exos) where ALKBH5 inhibition assay was conducted to verify their function in the biological characteristics of TNBC cells. Results: Bioinformatics analysis revealed 45 key genes of ALKBH5 regulating TNBC cell stemness. In addition, UBE2C was predicted as a key downstream gene and p53 was predicted as a downstream signaling of ALKBH5. In vivo data confirmed that ALKBH5 upregulated UBE2C expression by regulating the m6A modification of UBE2C and reduced p53 expression, thus promoting the stemness, growth and metastas