Function And Mechanism Analysis Of Uhrf2 In Mice Colorectal Cancer Tumorgenesis

Colorectal Cancer,with higher morbidity and higher mortality,has been the world’s third largest malignant cancer.Ubiquitin-like with PHD and ring finger domains 2（Uhrf2）gene encodes a nucleoprotein that can play a key role in cell cycle regulation and epigenetics with mulple structure domains.Overespression of UHRF2 can cause G1 phase cell cycle arrest.All together,it suggests that Uhrf2 may play an important role in colorectal cancer.However,Uhrf2,as a newly discovered gene,its functions and mechanism in the occurrence and development of colorectal cancer are not clear so far.We generated the Uhrf2-LacZ reporter mice,and using CRISPR/Cas9 genome editing technology,we generated the Uhrf2^-/-and ApcMin Uhrf2^-/-mice.By X-gal dying,we found that Uhrf2 is expressed enriched in the intestinal crypt stem cell region and the transit amplifying cell region,suggestting that it may be associated with intestinal epithelial cell proliferation.And the histological morphological analysis also showed that knockout Uhrf2 has no influence on the histological and morphology.Sequentially,we showed that knockout Uhrf2 can inhibit the the occurrence and development of tumor by comparing the number,the distribution in proximal/middle/distal intestine,and the diameter size of polyps in the 5 months old ApcMin/-mouse and the ApcMin/-hrf2-/-mouse.Further,by slicing the microadenomas in per Swiss roll section of the entire small intestine,we confirmed that the Uhrf2 knockout can inhibit the early stage of the intestinal tumorigenesis.We also explored the mechanism of knockout of Uhrf2 inhibiting the occurrence and development of colorectal cancer.Knockout Uhrf2 dose not affect the stead-state maintains of the intestinal epithelium and damage repair but intestinal tumorigenesis,suggest Uhrf2 is a potential drug target for colorectal cancer treatment.