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Updated: Aug 7, 2025

Molecular Profiling of the Invasive Tumor Microenvironment in a 3-Dimensional Model of Colorectal Cancer Cells and Ex vivo Fibroblasts
Published on: April 29, 2014
NAT10 mediated mRNA acetylation modification patterns associated with colon cancer progression and microsatellite
Hailin Zhang1,2, Wenqing Shan1,2, Zhenwei Yang1,2
1Department of Gastroenterology, Zhongnan Hospital of Wuhan University, Wuhan, Hubei, China.
Abstract:
N4-acetylcytidine (ac4C) is one type of RNA modification found in eukaryotes. RNA acetylation modifications are gradually expanding in oncology. However, the role of RNA acetylation modifications in colorectal cancer and its association with colorectal cancer microsatellite status remain unclear. Using public databases and in vitro experiments, we verified the expression and biological function of NAT10, as the key RNA acetylation modification enzyme, in colorectal cancer. The results showed that NAT10 was highly expressed in colorectal cancer, and significantly promoted colorectal cancer cell proliferation. NAT10 was also involved in several aspects of cell homoeostasis such as ion transport, calcium-dependent phospholipid binding, and RNA stability. NAT10 expression positively correlated with immune infiltration in colorectal cancer. We further constructed a risk regression model for mRNA acetylation in colorectal cancer using acetylation-related differential genes. We found that tumour immune infiltration, microsatellite instability (MSI) proportion, tumour immune mutation burden, and patient response to immunotherapy were positively correlated with risk scores. For the first time, our study showed that the level of mRNA acetylation modification level is elevated in colorectal cancer and positively correlates with immune infiltration and microsatellite status of patients. Based on our findings, NAT10 may be a new target for colorectal cancer treatment.
Insights
N4-acetylcytidine (ac4C) RNA acetylation is elevated in colorectal cancer, promoting cell proliferation. This modification correlates with immune infiltration and microsatellite status, suggesting NAT10 as a potential therapeutic target.
Area of Science:
- Biochemistry
- Molecular Biology
- Oncology
Background:
- N4-acetylcytidine (ac4C) is an RNA modification found in eukaryotes.
- RNA acetylation's role in colorectal cancer and its association with microsatellite status are not well understood.
Purpose of the Study:
- To investigate the expression and function of NAT10, a key RNA acetylation enzyme, in colorectal cancer.
- To explore the correlation between RNA acetylation, immune infiltration, and microsatellite status in colorectal cancer.
Main Methods:
- Utilized public databases and in vitro experiments to analyze NAT10 expression and function.
- Constructed a risk regression model based on acetylation-related differential genes in colorectal cancer.
Main Results:
- NAT10 was highly expressed in colorectal cancer, promoting cell proliferation and influencing ion transport, calcium-dependent phospholipid binding, and RNA stability.
- NAT10 expression positively correlated with immune infiltration in colorectal cancer.
- Risk scores derived from mRNA acetylation positively correlated with tumor immune infiltration, microsatellite instability (MSI), tumor mutational burden, and immunotherapy response.
Conclusions:
- mRNA acetylation levels are elevated in colorectal cancer and correlate with immune infiltration and microsatellite status.
- NAT10 may serve as a novel therapeutic target for colorectal cancer treatment.
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