Novel evidence for m6A methylation regulators as prognostic biomarkers and FTO as a potential therapeutic target in gastric cancer

Author(s):  
Tadanobu Shimura ◽  
Raju Kandimalla ◽  
Yoshinaga Okugawa ◽  
Masaki Ohi ◽  
Yuji Toiyama ◽  
...  
2020 ◽  
Author(s):  
Yoshimi Yasukawa ◽  
Naoko Hattori ◽  
Naoko Iida ◽  
Hideyuki Takeshima ◽  
Masahiro Maeda ◽  
...  

Abstract Cancer-associated fibroblasts (CAFs) tend to have tumor-promoting capacity, and can provide therapeutic targets. Even without cancer cells, CAF phenotypes are stably maintained, and DNA methylation and H3K27me3 changes have been shown to be involved. Here, we searched for a potential therapeutic target in primary CAFs from gastric cancer and a mechanism for its dysregulation. Expression microarray using eight CAFs and seven non-CAFs (NCAFs) revealed that serum amyloid A1 (SAA1), which encodes an acute phase secreted protein, was second most upregulated in CAFs, following IGF2. Conditioned medium (CM) derived from SAA1-overexpressing NCAFs was shown to increase migration of gastric cancer cells compared to that from control NCAFs, and its tumor-promoting effect was comparable to that of CM from CAFs. In addition, increased migration of cancer cells by CM from CAFs was mostly canceled with CM from CAFs with SAA1 knockdown. Chromatin immunoprecipitation (ChIP)-quantitative PCR showed that CAFs had higher levels of H3K27ac, an active enhancer mark, in the promoter and the two far upstream regions of SAA1 than NCAFs. Also, BET bromodomain inhibitors, JQ1 and mivebresib, decreased SAA1 expression and tumor-promoting effects in CAFs, suggesting SAA1 upregulation by enhancer activation in CAFs. Our present data showed that SAA1 is a candidate therapeutic target from gastric CAFs and indicated that increased enhancer acetylation is important for its overexpression.


EBioMedicine ◽  
2021 ◽  
Vol 69 ◽  
pp. 103436
Author(s):  
Fangyuan Li ◽  
Jianfang Li ◽  
Junxian Yu ◽  
Tao Pan ◽  
Beiqin Yu ◽  
...  

Tumor Biology ◽  
2014 ◽  
Vol 35 (12) ◽  
pp. 12737-12742 ◽  
Author(s):  
Hongying Zhang ◽  
Buxian Tian ◽  
Hongyu Yu ◽  
Hongyue Yao ◽  
Zhian Gao

2019 ◽  
Vol 235 (3) ◽  
pp. 2738-2752 ◽  
Author(s):  
Feifei Ren ◽  
Qitai Zhao ◽  
Bin Liu ◽  
Xiangdong Sun ◽  
Youcai Tang ◽  
...  

Sign in / Sign up

Export Citation Format

Share Document