AUTHOR=Liu Yuan-Yuan , Ding Cheng-Zhi , Chen Jia-Ling , Wang Zheng-Shuai , Yang Bin , Wu Xiao-Ming 

TITLE=A Novel Small Molecular Inhibitor of DNMT1 Enhances the Antitumor Effect of Radiofrequency Ablation in Lung Squamous Cell Carcinoma Cells

JOURNAL=Frontiers in Pharmacology

VOLUME=Volume 13 - 2022

YEAR=2022

URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2022.863339

DOI=10.3389/fphar.2022.863339

ISSN=1663-9812

ABSTRACT=Radiofrequency ablation (RFA) is a relatively new and effective therapeutic strategy for treating lung squamous cell carcinomas (LSCCs). However, RFA is rarely used in the clinic for LSCC which still suffers from a lack of effective comprehensive treatment strategies. In the presence work, we investigate iDNMT, a novel small molecular inhibitor of DNMT1 with a unique structure. In clinical LSCC specimens, endogenous DNMT1 was positively associated with methylation rates of miR-27-3p’s promoter. Moreover, endogenous DNMT1 was negatively correlated with miR-27-3p expression which targets PSEN-1, the catalytic subunit of γ-secretase which mediates the cleavage and activation of the Notch pathway. We found that DNMT1 increased activation of the Notch pathway in clinical LSCC samples while downregulating miR-27-3p expression and hypermethylation of miR-27-3p’s promoter. As well as inhibiting activation of the Notch pathway by repressing methylation of the miR-27-3p promoter, treatment of LSCC cells with iDNMT1 also enhanced the sensitivity of LSCC tumor tissues to RFA treatment. Herein, these data suggest that iDNMT-induced inhibition of DNMT-1 enhances miR-27-3p expression in LSCC to inhibit activation of the Notch pathway. Further, the combination of iDNMT and RFA may be a promising therapeutic strategy for LSCC.