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

Abstract

Our previous study clarified the carcinogenic properties of arginine-specific mono-ADP-ribosyltransferase 1 (ART1), which results in a critical post-translational modification that changes the structure and function of proteins and is widely involved in important processes. This study provides, for the first time, a comprehensive transcriptomic analysis of colorectal cancer cells with ART1 silencing by Illumina RNA-Seq and related verification experiments. Lentiviral infection was used to construct a CT-26 cell line with stable knockdown of the ART1 gene, and a whole transcriptome sequencing technique was performed to identify differentially expressed genes (DEGs). GO and KEGG classification/enrichment analyses and verification experiments were performed to determine the role of ART1 in the progression of colorectal cancer. A total of 5552 DEGs, GO functions and KEGG pathways with the highest enrichment, various SNPs, and diverse splicing patterns were identified. Importantly, knockdown of ART1 affected the splicing of certain key genes related to tumor cell growth and downregulated the expression of the key gene PTBP1 for alternative splicing. The overall attenuation of the endoplasmic reticulum unfolded protein response (UPR) signaling pathway caused by the inhibition of mono-ADP-ribosylation of GRP78 could disrupt UPR signaling, leading to the occurrence of apoptosis to impede tumorigenesis. ART1, which is clustered in organelles, may promote the development of colorectal cancer by participating in a variety of new mechanisms, including endoplasmic reticulum stress regulation and alternative splicing, and may be a good clinical drug target for targeted therapy of CRC.

• Authors: Shuxian Zhang, Jiale Duan, Yanping Yang, Hanjuan Gong, Yi Tang, Ming Xiao, Ming Li, Qingshu Li, Yalan Wang
• Journal: Medical oncology (Northwood, London, England) (Med Oncol) Vol. 38 Issue 9 Pg. 111 (Aug 06 2021) ISSN: 1559-131X [Electronic] United States
• PMID: 34357465 (Publication Type: Journal Article)
• Copyright: © 2021. Springer Science+Business Media, LLC, part of Springer Nature.

Chemical References

• Biomarkers, Tumor
• Heterogeneous-Nuclear Ribonucleoproteins
• Ptbp1 protein, mouse
• Polypyrimidine Tract-Binding Protein
• ADP Ribose Transferases

Topics

• ADP Ribose Transferases (genetics, metabolism)
• ADP-Ribosylation
• Animals
• Apoptosis
• Biomarkers, Tumor (genetics, metabolism)
• Cell Proliferation
• Colonic Neoplasms (drug therapy, metabolism, pathology)
• Gene Expression Regulation, Neoplastic
• Heterogeneous-Nuclear Ribonucleoproteins (genetics, metabolism)
• Mice
• Mice, Inbred BALB C
• Polypyrimidine Tract-Binding Protein (genetics, metabolism)
• Signal Transduction
• Transcriptome
• Tumor Cells, Cultured