Skip to Content
MilliporeSigma
  • Targeted demethylation of the SARI promotor impairs colon tumour growth.

Targeted demethylation of the SARI promotor impairs colon tumour growth.

Cancer letters (2019-02-17)
Qin Wang, Lei Dai, Yuan Wang, Jie Deng, Yi Lin, Qingnan Wang, Chao Fang, Zida Ma, Huiling Wang, Gang Shi, Lin Cheng, Yi Liu, Shuang Chen, Junshu Li, Zhexu Dong, Xiaolan Su, Lie Yang, Shuang Zhang, Ming Jiang, Meijuan Huang, Yang Yang, Dechao Yu, Zongguang Zhou, Yuquan Wei, Hongxin Deng
PMID30771439
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.