Genome-wide identification of alternative splicing related with transcription factors and splicing regulators in breast cancer stem cells responding to fasting-mimicking diet

Abstract

Fasting-mimicking diet (FMD) can effectively inhibit the viability of breast cancer stem cells (CSCs). However, the molecular mechanisms underlying the inhibitory function of FMD on breast CSCs remain largely unknown. Elucidating the mechanisms by which FMD suppresses breast CSCs is beneficial to targeting breast CSCs. Herein, we systematically analyze alternative splicing and RNA binding protein (RBP) expression in breast CSCs during FMD. The analysis results show that a large number of regulated alternative splicing (RAS) and differentially expressed genes (DEGs) appear responding to FMD. Further studies show that there are potential regulatory relationships between transcription factors (TFs) with RAS (RAS-TFs) and their differentially expressed target genes (RAS-TF-DEGs). Moreover, differentially expressed RNA binding proteins (DERBPs) exhibit potential regulatory functions on RAS-TFs. In short, DERBPs potentially control the alternative splicing of TFs (RAS-TFs), regulating their target gene (RAS-TF-DEG) expression, which leads to the regulation of biological processes in breast CSCs during FMD. In addition, the alternative splicing and DEGs are compared between breast CSCs and differentiated cancer cells during FMD, providing new interpretations for the different responses of the two types of cells. Our studies will shed light on the understanding of the molecular mechanisms underlying breast CSC inhibition induced by FMD.