| Literature DB >> 30771439 |
Qin Wang1, Lei Dai2, Yuan Wang1, Jie Deng1, Yi Lin1, Qingnan Wang1, Chao Fang3, Zida Ma3, Huiling Wang1, Gang Shi1, Lin Cheng1, Yi Liu1, Shuang Chen1, Junshu Li1, Zhexu Dong1, Xiaolan Su1, Lie Yang3, Shuang Zhang4, Ming Jiang4, Meijuan Huang4, Yang Yang1, Dechao Yu1, Zongguang Zhou3, Yuquan Wei1, Hongxin Deng5.
Abstract
SARI (suppressor of activator protein 1, regulated by IFN) functions as a tumour suppressor and is inactivated in various cancers. However, the mechanism underlying SARI inactivation in cancer remains elusive. In this study, we detected a high level of DNA methylation of the SARI promoter and an inverse correlation between SARI promoter methylation and expression in malignant tissues from patients with colon cancer. Furthermore, we found that the SARI promoter methylation status is a prognostic indicator for patients with colon cancer. A dCas9-multiGCN4/scFv-TET1CD-sgRNA-based SARI-targeted demethylation system (dCas9-multiGCN4/scFv-TET1CD-sgSARI) was constructed to precisely and specifically demethylate regions of SARI; this system resulted in the substantial activation of SARI expression. Further in vitro and in vivo data confirmed that dCas9-multiGCN4/scFv-TET1CD-sgSARI exerts anti-tumour effects by regulating tumour proliferation, apoptosis, and angiogenesis. Collectively, specific demethylation of the SARI promoter and restoration of endogenous SARI expression by dCas9-multiGCN4/scFv-TET1CD-SARI have therapeutic applications for colon cancer and perhaps for other cancers.Entities:
Keywords: Colon cancer; Methylation; SARI; TET1; dCas9
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Year: 2019 PMID： 30771439 DOI： 10.1016/j.canlet.2019.01.040
Source DB: PubMed Journal: Cancer Lett ISSN： 0304-3835 Impact factor: 8.679