Identification of histone methyltransferase NSD2 as an important oncogenic gene in colorectal cancer

• DOI: 10.1038/s41419-021-04267-6
• Publication Date: 2021-10-20T19:18:29Z
• Authors: Li-hao Zhao; Quan Li; Zhi-Jun Huang; Mi-Xue Sun; Jing-jing Lu; Xiao-hua Zhang; Gang Li; Fang Wu
• Keywords: Ectopic expression

Colorectal cancer (CRC) is the second common cause of cancer-related human mortalities. Dysregulation histone 3 (H3) methylation could lead to transcriptional activation multiple oncogenes, which closely associated with CRC tumorigenesis and progression. Nuclear receptor-binding SET Domain protein 2 (NSD2) a key methyltransferase catalyzing H3 lysine 36 dimethylation (H3K36me2). Its expression, potential functions, molecular mechanisms in are studied here. Gene Expression Profiling Interactive Analysis (GEPIA) bioinformatics results showed that NSD2 mRNA expression elevated both colon cancers rectal cancers. Furthermore, levels local tissues significantly higher than those matched surrounding normal tissues. In primary cells established cell lines, shRNA-induced silencing or CRISPR/Cas9-induced knockout inhibited viability, proliferation, cycle progression, migration, invasion. shRNA induced mitochondrial depolarization, DNA damage, apoptosis cells. Contrarily, ectopic overexpression further enhanced H3K36me2, expressions oncogenes (ADAM9, EGFR, Sox2, Bcl-2, SYK, MET) Akt were decreased after Their however increased overexpression. A catalytic inactive (Y1179A) also activation, as well proliferation migration vivo, intratumoral injection adeno-associated virus (AAV)-packed largely xenograft growth nude mice. Together, exerted oncogenic functions be promising therapeutic target.