| Literature DB >> 35489200 |
Hironao Nakayama1, Hidetaka Ohnuki2, Masako Nakahara3, Hisayo Nishida-Fukuda4, Tomohisa Sakaue5, Shinji Fukuda6, Shigeki Higashiyama7, Yuki Doi8, Masahiro Mitsuyoshi9, Takashi Okimoto10, Giovanna Tosato2, Chiaki Kusumoto11.
Abstract
Netrin-1, the protein product of the NTN1 gene, is an axon guidance molecule implicated in regulation of cell survival and tumorigenesis. Expression of the netrin-1 receptors deleted in colorectal cancer (DCC) and uncoordinated 5 homolog (UNC5H) is frequently silenced in colorectal cancer (CRC) by either loss of heterozygosity or epigenetic mechanisms. However, netrin-1 expression and regulation in CRC are mostly unknown. Here, we report that NTN1 expression is significantly reduced in most CRC tissues compared to the adjacent normal intestinal mucosa, and that NTN1 DNA methylation is significantly higher in CRCs (24.6%) than in the adjacent normal intestinal mucosa (4.0%). In 6 CRC cell lines, NTN1 expression is low. Treatment with 5-Aza-2'-deoxycytidine increased expression of NTN1 in CRC cell lines, indicating that DNA methylation represses NTN1 transcription in CRCs. NTN1 DNA hypermethylation was significantly associated with advanced CRC disease. Median netrin-1 serum levels were significantly decreased in CRC patients (330.1 pg/mL) compared with normal individuals (438.6 pg/mL). Our results suggest that netrin-1 is a candidate biomarker for CRC.Entities:
Keywords: Axon guidance; Colorectal cancer; DNA methylation; Netrin-1; VEGF-A
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Year: 2022 PMID： 35489200 PMCID： PMC9155250 DOI： 10.1016/j.bbrc.2022.04.069
Source DB: PubMed Journal: Biochem Biophys Res Commun ISSN： 0006-291X Impact factor: 3.322