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Molecular targets of colorectal cancer transformation revealed by single-cell sequencing

ABSTRACT: Ulcerative colitis (UC) is associated with a significant risk of colorectal cancer transformation, which is considered one of its major complications. Prolonged chronic inflammation in the colon mucosa can lead to carcinogenesis due to various factors including dysregulation of cell proliferation and apoptosis, abnormal activation of the immune system, as well as DNA damage and repair abnormalities. Furthermore, the release of inflammatory mediators may directly or indirectly promote the formation and growth of cancer cells. The AOM/DSS mouse model is widely utilized to mimic the process of human colorectal cancer development, including chronic inflammation, carcinogenesis, and tumor progression. The model involves the administration of azoxymethane (AOM), a carcinogenic substance that induces DNA mutations and damage in colonic epithelial cells, leading to the initiation of colorectal cancer. Subsequently, dextran sulfate sodium (DSS), a chemical compound that induces intestinal inflammation, is administered through drinking water. The mice are subjected to cycles of DSS treatment interspersed with recovery periods, during which colitis-associated colorectal tumorigenesis occurs. The assessment typically involves monitoring of colon length, tumor formation, and histopathological examination. The mechanisms underlying colorectal cancer transformation in UC remain incompletely understood. However, research suggests that controlling inflammation, implementing standardized treatment protocols, and regular surveillance through colonoscopy and follow-up are crucial for both prevention and early detection of carcinogenesis. Therefore, further investigations into the mechanisms of colorectal cancer transformation in UC and the development of novel prevention and treatment strategies are essential for improving the prognosis and quality of life of UC patients.

ORGANISM(S): Mus musculus

PROVIDER: GSE264607 | GEO | 2025/12/04

REPOSITORIES: GEO

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Project description:Nonresolving inflammation is correlated to carcinogenesis. Ulcerative colitis-associated colorectal cancer (UC-CRC), one of the typical carcinoma generated by inflammation that cannot be resolved properly, has been widely believed to involve a multistep process contains M-bM-^@M-^\inflammation-dysplasia-cancerM-bM-^@M-^] sequence. The exact molecular mechanisms underlying the step-wise development of UC-CRC is still not fully understood. Detecting the changes in gene expression profiles may help to reveal why and how does the prolonged inflammatory response lead to carcinogenesis, and to characterize potential diagnostic/prognostic markers or additional therapeutic targets for UC-CRC. There for, we performed temporal genome expression profiling analysis using the Affymetrix genome wide microarray system to identify broad scale changes in gene expression associated with the development of colitis-associated cancer, based on an AOM/DSS induced mouse model of UC-CRC. 6-week-old male ICR mice were given a single intraperitoneal injection of AOM (10mg/kg) at Day 1, followed by three cycles of DSS administration (cycle 1: 2%, Day 8~14; cycle 2: 1.5%, Day 29~33; cycle 3: 1.5%, Day 50~54) in the drinking water. Instead, control group of mice were given a single intraperitoneal injection of saline (10mg/kg) at Day 1 and distilled water drinking from the beginning to the end without DSS. Colorectal tissues were collected at days 14, 28, 42, 56 and 140 (at the end of the 2nd, 4th, 6th, 8th and 20th week) from the AOM/DSS group and at day 14 from the control group. Pathological changes of each sample were identified under microscope. Samples collected at the end of the 2nd week were inflamed mucosae, the 4th week were low grade dysplasias, the 6th week were high grade dysplasias, the 8th week were high grade dysplasias with active inflammation, the 20th week were carcinomas, and the control sample were normal mucosae. Total RNA were extracted and detected by Affymerix GeneChip Mouse Genome 430 2.0 Array.

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Molecular targets of colorectal cancer transformation revealed by single-cell sequencing

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