The pleiotropic enhancer enh9 promotes cell proliferation and migration in non-small cell lung cancer via ERMP1 and PD-L1

Qilin Wang; Junyou Zhang; Yanling Wen; Sihan Qi; Yingying Duan; Qian Liu; Chunyan Li

doi:10.1016/j.bbadis.2023.167015

The pleiotropic enhancer enh9 promotes cell proliferation and migration in non-small cell lung cancer via ERMP1 and PD-L1

Biochim Biophys Acta Mol Basis Dis. 2024 Mar;1870(3):167015. doi: 10.1016/j.bbadis.2023.167015. Epub 2024 Jan 4.

Authors

Qilin Wang¹, Junyou Zhang¹, Yanling Wen², Sihan Qi¹, Yingying Duan¹, Qian Liu¹, Chunyan Li³

Affiliations

¹ School of Engineering Medicine, Beihang University, Beijing 100191, China; Key Laboratory of Big Data-Based Precision Medicine (Ministry of Industry and Information Technology), Beihang University, Beijing 100191, China; School of Biological Science and Medical Engineering, Beihang University, Beijing 100191, China.
² Institute for Hepatology, National Clinical Research Center for Infectious Disease, Shenzhen Third People's Hospital, Shenzhen, Guangdong 518112, China; The Second Affiliated Hospital, School of Medicine, Southern University of Science and Technology, Shenzhen, Guangdong 518112, China.
³ School of Engineering Medicine, Beihang University, Beijing 100191, China; Key Laboratory of Big Data-Based Precision Medicine (Ministry of Industry and Information Technology), Beihang University, Beijing 100191, China; School of Biological Science and Medical Engineering, Beihang University, Beijing 100191, China; Beijing Advanced Innovation Center for Big Data-Based Precision Medicine, Beihang University, Beijing 100191, China. Electronic address: lichunyan@buaa.edu.cn.

PMID: 38182069
DOI: 10.1016/j.bbadis.2023.167015

Abstract

Enhancers, cis-acting DNA elements for transcriptional regulation, are important regulators of cell identity and disease. However, of the hundreds of thousands of enhancers annotated in the human genome, only a few have been studied for their regulatory mechanisms and functions in cancer progression and therapeutic resistance. Here, we report the pleiotropy of one enhancer (named enh9) in both cell proliferation and migration in non-small cell lung cancer (NSCLC) cells. By integrating multi-genomic data, ERMP1 and PD-L1 were screened out as potential targets of enh9. CUT&Tag sequencing demonstrated that enh9 was involved in the genomic interactions between the transcription factor RELA and the promoters of ERMP1 and PD-L1. In addition, ERMP1 and PD-L1 were validated to be involved in cell proliferation and migration, respectively. Our study fully elucidated the function and transcriptional regulation mechanisms of enh9 in NSCLC. The exploration on enhancers is promising to provide new insights for cancer diagnosis and therapy.

Keywords: Enhancer; Migration; Non-small cell lung cancer; Pleiotropy; Proliferation.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

B7-H1 Antigen / genetics
Carcinoma, Non-Small-Cell Lung* / drug therapy
Carcinoma, Non-Small-Cell Lung* / genetics
Cell Proliferation / genetics
Humans
Lung Neoplasms* / drug therapy
Lung Neoplasms* / genetics
Promoter Regions, Genetic

Substances

B7-H1 Antigen