Syntaxin Binding Protein 1 regulates the alternative splicing events related to DNA repair in MDA-MB-231cells

Breast cancer has emerged as a prevalent form of cancer globally, particularly triple-negative breast cancer. The high prevalence and malignant characteristics of this condition are associated with a variety of environmental factors and molecular influences. Syntaxin Binding Protein 1 (STXBP1) is a transmembrane transport protein predominantly expressed in the brain, playing a crucial role in regulating neurotransmitter release. The low expression levels of STXBP1 are positively correlated with poor prognosis of breast cancer. However, the mechanisms by which STXBP1 contributes to the development of breast cancer remain unclear. In this study, we conducted an overexpression of STXBP1 in triple-negative breast cancer cells (MDA-MB-231) and subsequently assessed its impact on cellular characteristics. Following this, we employed transcriptome sequencing (RNA-seq) technology to investigate the downstream targets associated with STXBP1 overexpression. In MDA-MB-231 cells, the overexpression of STXBP1 significantly inhibited cell proliferation and enhanced apoptosis levels. Through an analysis of RNA sequencing data, we discovered that STXBP1 globally regulates both the expression and alternative splicing profile in MDA-MB-231 cells by modulating 111 differentially expressed genes (DEGs) and 1161 regulated alternative splicing events (RASEs). STXBP1 plays a crucial role in regulating the splicing patterns of numerous DNA repair-related genes, including USP48 and PLEC. Finally, we validated the expression changes of these genes and alternative splicing events in key pathways through RT-qPCR analysis. In addition, we conducted an overlap analysis on the transcriptome data of radiotherapy breast cancer cells alongside our own dataset, which revealed 21 differential alternative splicing events. Notably, this includes the DNA repair-related gene UBE21, whose expression patterns were corroborated by RT-qPCR experiments. We speculate that STXBP1 may play a role in the radiation resistance process of triple-negative breast cancer (TNBC) by regulating the alternative splicing of genes associated with DNA repair. To summarize, this study thoroughly investigated the downstream targets and functions of STXBP1 in breast cancer cells, elucidating the molecular mechanisms underlying STXBP1's anti-tumor properties in relation to breast cancer. These molecular targets have the potential to serve as promising avenues for the treatment of breast cancer, particularly in the case of triple-negative breast cancer.