Tumor suppressor genes are reactivated by miR-26A1 via enhancer reprogramming in NSCLC

Author:

Li Hongling1ORCID,Da Dezhuan1,Yu Wenqiang2,Chen Lu2,Yang Shuai2,Zhang Baolong2,Wang Yongying1,Li Linyu1,Dang Chunyan1

Affiliation:

1. Department of Oncology, Gansu Provincial Hospital, The First Clinical Medical College of Gansu University of Chinese Medicine , Lanzhou 730000 , PR China

2. Institutes of Biomedical Sciences, Shanghai Medical College, Fudan University , Shanghai 200000 , PR China

Abstract

Abstract 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.

Funder

National Natural Science Foundation of China

Science and Technology Program of Gansu Program

Internal Scientific Research Foundation of Gansu Provincial Hospital

Publisher

Oxford University Press (OUP)

Subject

Genetics (clinical),Genetics,Molecular Biology,General Medicine

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