文献类型：期刊文献

英文题名：Tumor suppressor genes are reactivated by miR-26A1 via enhancer reprogramming in NSCLC

作者：Li, Hongling[1];Da, Dezhuan[1];Yu, Wenqiang[2];Chen, Lu[2];Yang, Shuai[2];Zhang, Baolong[2];Wang, Yongying[1];Li, Linyu[1];Dang, Chunyan[1]

第一作者：李海龙

通信作者：Li, HL[1]

机构：[1]Gansu Univ Chinese Med, Clin Med Coll 1, Gansu Prov Hosp, Dept Oncol, Lanzhou, Peoples R China;[2]Fudan Univ, Shanghai Med Coll, Inst Biomed Sci, Shanghai 200000, Peoples R China

第一机构：甘肃中医药大学

通信机构：[1]corresponding author), Gansu Prov Hosp, Dept Oncol, Lanzhou 730000, Peoples R China.

年份：0

外文期刊名：HUMAN MOLECULAR GENETICS

收录：;WOS:【SCI-EXPANDED(收录号:WOS:000850871300001)】；

基金：ThisworkwassupportedbyNationalNaturalScienceFoundationofChina[grantnumber81760537,81560498], ScienceandTechnologyProgramofGansuProgram[grantnumber20YF8WA096] andInternalScientificResearchFoundationofGansuProvincialHospital[grantnumber19SYPYA3].

语种：英文

摘要：Non-small cell lung cancer (NSCLC) is one of the most malignant epithelial tumors. Studies have suggested that DNA hypermethylation of promoters and abnormal histone modifications could induce tumor suppressor genes (TSGs) downregulation in NSCLC. However, the exact mechanism of TSGs downregulation remains unclear. In this study, we found that there is no difference in the regions of most TSGs promoters in NSCLC. Moreover, we found that there is no DNA methylation difference in the region of VILL promoter in NSCLC compared with adjacent tissue samples by pyrosequencing. We further demonstrated that VILL was markedly reactivated in A549 and H1703 cells infected with miR-26A1 lentivirus while this activation was inhibited by JQ1, an enhancer inhibitor. In addition, we identified that miR-26A1 could function as a tumor suppressor to inhibit proliferation and metastasis of NSCLC cells. Chromatin immunoprecipitation assays revealed that overexpression of miR-26A1 could significantly induce the enrichment of H3K27ac at the enhancer regions in A549 cells. To sum up, our findings revealed that enhancer-mediated TSGs regulation occured in NSCLC, suggesting that miR-26A1 could serve as a key regulator and may be a potential therapeutic target for NSCLC.