Elevated colorectal cancer risk in the hnRNP I knockout mice treated with azoxymethane/dextran sulfate sodium

Chronic inflammation and increased epithelial proliferation play an important role in the development of colorectal cancer (CRC), which is one of the most common and lethal cancers worldwide. HnRNP I is an RNA-binding protein that plays an important role in post-transcriptional regulation of gene expression and intestinal barrier function. In this study, hnRNP I knockout (KO) mice of and AOM/DSS chemical induction model were used to investigate the molecular mechanism of hnRNP I deficiency on colon epithelial dysplasia and early carcinogenesis. The results showed that the hnRNP I knockout mice showed significant weight loss and increased disease activity index (DAI) during AOM/DSS treatment. Abnormal crypt foci (ACF) and dysplasia were found in mice. In addition, elevated nuclear β-catenin localization was observed, strongly suggesting Wnt pathway induction. Moreover, the population of goblet cells was significantly decreased, indicating impaired epithelial barrier integrity and heightened mucosal injury. Ki-67 mislocalization indicated abnormal cell proliferation, which was associated with disruption of recess homeostasis. Our results provide strong evidence that loss of hnRNP I lead to a disruption of epithelial proliferation compartmentalization prevents secretory cell differentiation, and drives aberrant Wnt signaling. It indicates a strong correlation between this loss and the direct stimulation of colonic epithelial dysplasia and the initiation of tumors. Collectively, these findings indicate that hnRNP I is an important regulator of intestinal epithelial homeostasis and suppresses tumor development. These findings provide new insights into the molecular mechanisms of inflammation-driven colorectal cancer and establish a theoretical basis for potential intervention approaches that target the hnRNP I regulatory network to inhibit precancerous lesions.

Name thesis:degree_name

M.S.

Level thesis:degree_level

Thesis

Discipline thesis:degree_discipline

Food Science & Human Nutrition

Grantor

University of Illinois Urbana-Champaign

Year dc:date

2025

Author dc:creator

• Zhang, Hehe

Contributors dc:contributor

• Pan, Yuan-Xiang
• Chen, Hong
• Mei, Wenyan

• hnRNP I Knockout Mice
• early-stage tumorigenesis
• AOM/DSS treatment

Statement dc:rights

• Copyright 2025 Hehe Zhang

Language dc:language

en, eng

Handle dc:identifier

https://hdl.handle.net/2142/129288

OAI record oai:identifier

https://www.ideals.illinois.edu/oai-pmh?verb=GetRecord&metadataPrefix=etdms&identifier=oai%3Awww.ideals.illinois.edu%3A2142%2F129288