Research Papers:

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

Yu-Han Hu, Qing Chen, Yan-Xia Lu, Jian-Ming Zhang, Chun Lin, Fan Zhang, Wen-Juan Zhang, Xiao-Min Li, Wei Zhang and Xue-Nong Li _

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Oncotarget. 2017; 8:46191-46203. https://doi.org/10.18632/oncotarget.17580

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Yu-Han Hu1,2,*, Qing Chen3,*, Yan-Xia Lu1,*, Jian-Ming Zhang1,3, Chun Lin1, Fan Zhang1, Wen-Juan Zhang1, Xiao-Min Li1, Wei Zhang1 and Xue-Nong Li1

1Department of Pathology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, China

2Department of Pathology, Xinxiang Medical University, Xinxiang, China

3Department of Surgery, Nanfang Hospital, Southern Medical University, Guangzhou, China

*These authors have contributed equally to this work

Correspondence to:

Xue-Nong Li, email: [email protected]

Keywords: NDN, LRP6, Wnt signaling pathway, colorectal cancer, proliferation

Received: December 22, 2016     Accepted: April 07, 2017     Published: May 03, 2017


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 facilitate the development of new therapeutic strategies against CRC.

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