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.

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Purpose Our previous study has clarified the carcinogenic properties of arginine-specific mono-ADP ribosyltransferase 1(ART1), which is considered to be 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 insight of transcriptomic analysis for colorectal cancer cells interfered with ART1 silencing by Illumina RNA-Seq and related verification experiments. Methods Lentiviral 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 classification/enrichment analysis and verification experiments were performed to determine the role of ART1 in the progression of colorectal cancer. Results a total of 5552 DEGs, GO function and KEGG pathway with highest enrichment, forms of SNP and diverse splicing patterns were able to be identified. Importantly, knockdown of ART1 affected the occurrence of the splicing of certain key genes related to tumor cell growth, also down-regulated 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. Conclusion ART1, 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.

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BackgroundIt is known that type 2 diabetes mellitus patients have higher susceptibility to colorectal cancer and poorer prognosis, but the mechanism is quite unknown. Here, we investigated effect of ADP-Ribosyltransferase 1 on growth of colorectal cancer combined diabetes in high norepinephrine status and the potential mechanism. MethodsWe evaluated size and weight of transplanted tumors with different ADP-Ribosyltransferase 1 level of CT26 cells or different norepinephrine level on diabetic mice model and observed their survival time as well. Consistently, CCK8 and flow cytometry were applied for detecting growth of CT26 cells in vitro. Western blot was performed for analyzing differentially expressed proteins of proliferatic profiles to determine ADP-Ribosyltransferase 1-modulated pathway.ResultsAccording to our data, high level of norepinephrine and ADP-Ribosyltransferase 1 both facilitated proliferation of CT26 cells in vitro and in vivo, besides, inhibition of norepinephrinee-depended-proliferation was observed in ADP-Ribosyltransferase 1 silencing CT26 cells in vitro compared with CT26 cells with ADP-Ribosyltransferase 1 expression. However, we discovered after reducing norepinephrine level of serum by surgery, size and weight of the transplanted tumors were significantly reduced compared with non-operated group and sham-operated group. Further, expression of ADP-Ribosyltransferase 1, mTOR, STAT3, p-AKT protein in tumor tissues of diabetic mice was increased rather than non-diabetes mice, while after depleting norepinephrine level by renal denervation operation, expression of proliferation-relative proteins mTOR, STAT3, p-AKT protein was decreased, but no change was discovered in ADP-Ribosyltransferase 1 expression. While under the same concentration of norepinephrine environment, ADP-Ribosyltransferase 1 boosts expression of p-AKT, mTOR, STAT3, CyclinD1 and c-myc in CT26 cells in vitro. ConclusionsThis study proposed a hypothesis that high-norepinephrine-induced proliferation of colorectal cancer required expression of ADP-Ribosyltransferase 1, and raise ADP-Ribosyltransferase 1 might be a candidate target for treatment of diabetes-associated colorectal cancer.