Silencing of CHFR Sensitizes Gastric Carcinoma to PARP Inhibitor Treatment.

CHFR is a tumor suppressor that not only recognizes poly(ADP-ribosylation) (PARylation) signals at the sites of DNA damage but also is downregulated in many types of cancer. However, the underlying mechanism linking its role in PARylation-mediated DNA damage repair and tumor suppression is unclear. Here, we examined a panel of gastric cancer cell lines as well as primary tissue samples from gastric cancer patients, and found that CHFR expression was silenced by DNA hypermethylation in gastric cancer including 38.46% of primary gastric cancers. DNMT1 was associated with aberrant methylation of CHFR, and the expression of CHFR was restored by DNMT1 inhibitor 5-aza-2-deoxycytidine (5-aza-CdR) treatment. Moreover, we found that loss of CHFR abolished DNA damage repair and sensitized gastric tumor cells to PARP inhibitor treatment. Thus, our study reveals a potential therapeutic approach for treating gastric cancer with PARP inhibitor and lacking CHFR can serve as a biomarker for predicting the efficacy of PARP inhibitor on the gastric tumor treatment in future.

Pubmed ID: 31812083