Hypermethylation of NDN promotes cell proliferation by activating the Wnt signaling pathway in colorectal cancer

Oncotarget
Yu-Han HuXue-Nong Li

Abstract

The progression of CRC is a multistep process involving several genetic changes or epigenetic modifications. NDN is a member of the MAGE family, encoding a protein that generally suppresses cell proliferation and acting as a transcriptional repressor. Immunohistochemical staining revealed that the expression of NDN was significantly down-regulated in CRC tissues compared with normal tissues and the down-regulation of NDN in CRC could reflect the hypermethylation of the NDN promoter. Treatment of the CRC cell line SW480 with the demethylating agent 5-Aza-CdR restored the NDN expression level. The down-regulation of NDN was closely related to poor differentiation, advanced TNM stage and poor prognosis of CRC. The inhibition of NDN promoted CRC cell proliferation by enriching cells in the S phase. Furthermore, we observed that NDN binds to the GN box in the promoter of LRP6 to attenuate LRP6 transcription and inhibit the Wnt signaling pathway in CRC. In conclusion, our study revealed that the hypermethylation of NDN promotes cell proliferation by activating the Wnt signaling pathway through directly increasing the transcription of LRP6 in CRC. These findings might provide a new theoretical basis for the pathogenesis of CRC and fac...Continue Reading

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Citations

Mar 19, 2019·Frontiers in Genetics·Ángeles Carlos-ReyesCésar López-Camarillo
Aug 28, 2020·Frontiers in Oncology·Susana Romero-GarciaAngeles Carlos-Reyes

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Datasets Mentioned

BETA
GSE25062
GSE40055

Methods Mentioned

BETA
ChIP
Flow-cytometry
xenograft
flow cytometry
PCR
reverse transcription PCR
transfection
Assay
immunoprecipitation

Software Mentioned

MethPrimer
Oncomine
SPSS13

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