Suppression of the NTS-CPS1 regulatory axis by AFF1 in lung adenocarcinoma cells

Junjie Yue; Qian Dai; Shaohua Hao; Shiqi Zhu; Xiaoxu Liu; Zhiqun Tang; Meng Li; Haitong Fang; Chengqi Lin; Zhuojuan Luo

doi:10.1016/j.jbc.2021.100319

Suppression of the NTS-CPS1 regulatory axis by AFF1 in lung adenocarcinoma cells

J Biol Chem. 2021 Jan-Jun:296:100319. doi: 10.1016/j.jbc.2021.100319. Epub 2021 Jan 22.

Authors

Junjie Yue¹, Qian Dai¹, Shaohua Hao¹, Shiqi Zhu¹, Xiaoxu Liu¹, Zhiqun Tang², Meng Li¹, Haitong Fang¹, Chengqi Lin³, Zhuojuan Luo⁴

Affiliations

¹ The Key Laboratory of Developmental Genes and Human Disease, School of Life Science and Technology, Southeast University, Nanjing, China.
² Singapore Eye research Institute, Singapore, Singapore.
³ The Key Laboratory of Developmental Genes and Human Disease, School of Life Science and Technology, Southeast University, Nanjing, China; Co-innovation Center of Neuroregeneration, Nantong University, Nantong, China. Electronic address: cqlin@seu.edu.cn.
⁴ The Key Laboratory of Developmental Genes and Human Disease, School of Life Science and Technology, Southeast University, Nanjing, China; Co-innovation Center of Neuroregeneration, Nantong University, Nantong, China. Electronic address: zjluo@seu.edu.cn.

Abstract

Upregulation of the neuropeptide neurotensin (NTS) in a subgroup of lung cancers has been linked to poor prognosis. However, the regulatory pathway centered on NTS in lung cancer remains unclear. Here we identified the NTS-specific enhancer in lung adenocarcinoma cells. The AF4/FMR2 (AFF) family protein AFF1 occupies the NTS enhancer and inhibits NTS transcription. Clustering analysis of lung adenocarcinoma gene expression data demonstrated that NTS expression is highly positively correlated with the expression of the oncogenic factor CPS1. Detailed analyses demonstrated that the IL6 pathway antagonizes NTS in regulating CPS1. Thus, our analyses revealed a novel NTS-centered regulatory axis, consisting of AFF1 as a master transcription suppressor and IL6 as an antagonist in lung adenocarcinoma cells.

Keywords: AFF1; enhancer; lung adenocarcinoma; neurotensin; transcription regulation.

Publication types

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

MeSH terms

A549 Cells
Adenocarcinoma of Lung / genetics*
Adenocarcinoma of Lung / pathology
Carbamoyl-Phosphate Synthase (Ammonia) / genetics*
Cell Proliferation / genetics
DNA-Binding Proteins / genetics*
Enhancer Elements, Genetic / genetics
Female
Gene Expression Regulation, Neoplastic / genetics
Humans
Interleukin-6 / genetics*
Male
Neurotensin / genetics*
Prognosis
Signal Transduction / genetics
Transcriptional Elongation Factors / genetics*

Substances

DNA-Binding Proteins
IL6 protein, human
Interleukin-6
Transcriptional Elongation Factors
AFF1 protein, human
Neurotensin
CPS1 protein, human
Carbamoyl-Phosphate Synthase (Ammonia)