Conditional knockout of the NSD2 gene in mouse intestinal epithelial cells inhibits colorectal cancer progression

Abstract

BackgroundNuclear receptor‐binding SET domain 2 (NSD2) is a histone methyltransferase, that catalyzes dimethylation of lysine 36 of histone 3 (H3K36me2) and is associated with active transcription of a series of genes. NSD2 is overexpressed in multiple types of solid human tumors and has been proven to be related to unfavorable prognosis in several types of tumors.MethodsWe established a mouse model in which the NSD2 gene was conditionally knocked out in intestinal epithelial cells. We used azoxymethane and dextran sodium sulfate to chemically induce murine colorectal cancer. The development of colorectal tumors were investigated using post‐necropsy quantification, immunohistochemistry, and enzyme‐linked immunosorbent assay (ELISA).ResultsCompared with wild‐type (WT) control mice, NSD2fl/fl‐Vil1‐Cre mice exhibited significantly decreased tumor numbers, histopathological changes, and cytokine expression in colorectal tumors.ConclusionsConditional knockout of NSD2 in intestinal epithelial cells significantly inhibits colorectal cancer progression.

Epithelial NSD2 maintains FMOs-mediated taurine biosynthesis to prevent intestinal barrier disruption

“…Further analysis revealed that a deficiency of NSD2 results in decreases of H3K36me2 at protein level and Fmo expression at mRNA level to impede taurine accumulation, both in vitro and in vivo. Several studies have shown the significant importance of NSD2 in chromatin regulation and regulates cell senescence, proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT) 19,[23][24][25][26][27][28][29][30][31][32][33][34][35][36] . Previous studies suggest that NSD2mediated H3K36me2 is crucial for transcription activation and the expression of multiple oncogenes in colorectal cancer (CRC) 25,30,37,38 .…”

“…Several studies have shown the significant importance of NSD2 in chromatin regulation and regulates cell senescence, proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT) 19,[23][24][25][26][27][28][29][30][31][32][33][34][35][36] . Previous studies suggest that NSD2mediated H3K36me2 is crucial for transcription activation and the expression of multiple oncogenes in colorectal cancer (CRC) 25,30,37,38 . These studies imply that NSD2, as a histone modifier, may play different roles depending on the genetic environment or context.…”