Identification of the role of mono-ADP-ribosylation in colorectal cancer by integrated transcriptome analysis

Abstract

Our previous study has clari ed the carcinogenic properties of arginine-speci c mono-ADP ribosyltransferase 1(ART1), which is considered to be a critical post-translational modi cation that changes the structure and function of proteins and is widely involved in important processes. This study provides, for the rst time, a comprehensive insight of transcriptomic analysis for colorectal cancer cells interfered with ART1 silencing by Illumina RNA-Seq and related veri cation experiments. MethodsLentiviral infection was used to construct a CT-26 cell line that stably knocks down the ART1 gene, a whole transcriptome sequencing technique was performed to identify differentially expressed genes (DEGs). GO and KEGG classi cation/enrichment analysis and veri cation experiments were performed to determine the role of ART1 in the progression of colorectal cancer. Resultsa total of 5552 DEGs, GO function and KEGG pathway with highest enrichment, forms of SNP and diverse splicing patterns were able to be identi ed. Importantly, knockdown of ART1 affected the occurrence of the splicing of certain key genes related to tumor cell growth, also downregulated expression of the key gene PTBP1 for alternative splicing. The overall attenuation of the endoplasmic reticulum unfolded protein response (UPR) signaling pathway caused by ART1 inhibition would unbalance UPR signaling, leading to the occurrence of apoptosis to impede tumorigenesis. ConclusionART1, which clustered in organelles, may promote the development of colorectal cancer by participating in a variety of new mechanisms including endoplasmic reticulum stress regulation, metabolic process or alternative splicing, which may provide a good clinical drug candidate closer to targeted therapy of CRC.