Downregulation of miR-4772-3p promotes enhanced regulatory T cell capacity in malignant pleural effusion by elevating Helios levels
10.1097/CM9.0000000000000517
- Author:
Wen-Qing YU
1
,
2
;
Ning-Fei JI
1
;
Cheng-Jing GU
3
;
Zhi-Xiao SUN
1
;
Zheng-Xia WANG
1
;
Zhong-Qi CHEN
1
;
Yuan MA
1
;
Zhen-Zhen WU
1
;
Yan-Li WANG
1
;
Chao-Jie WU
1
;
Ming-Dong DING
4
;
Gui-Hong DAI
5
;
Juan YAO
6
;
Rong-Rong JIN
5
;
Mao HUANG
1
;
Ming-Shun ZHANG
7
Author Information
1. Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029, China
2. Department of Infectious Diseases, Taizhou People’s Hospital Affiliated to Nantong University, Taizhou, Jiangsu 225300, China
3. Department of Pharmacy, Taizhou People’s Hospital Affiliated to Nantong University, Taizhou, Jiangsu 225300, China
4. Department of Infectious Diseases, Taizhou People’s Hospital Affiliated to Nantong University, Taizhou, Jiangsu 225300, China
5. Department of Pathology, Taizhou People’s Hospital Affiliated to Nantong University, Taizhou, Jiangsu 225300, China
6. Department of Oncology, Taizhou People’s Hospital Affiliated to Nantong University, Taizhou, Jiangsu 225300, China
7. Department of Immunology, Nanjing Medical University, Nanjing, Jiangsu 210029, China
- Publication Type:Journal Article
- Keywords:
Helios;
IKAROS family zinc finger 2;
Lung cancer;
Malignant pleural effusion;
MiR-4772-3p;
Regulatory T cells
- From:
Chinese Medical Journal
2019;132(22):2705-2715
- CountryChina
- Language:English
-
Abstract:
Background:Malignant pleural effusion (MPE) is a complicated condition of patients with advanced tumors. Further dissecting the microenvironment of infiltrated immune cells and malignant cells are warranted to understand the immune-evasion mechanisms of tumor development and progression.
Methods:The possible involvement of microRNAs (miRNAs) in malignant pleural fluid was investigated using small RNA sequencing. Regulatory T cell (Treg) markers (CD4, CD25, forkhead box P3), and Helios (also known as IKAROS Family Zinc Finger 2 [IKZF2]) were detected using flow cytometry. The expression levels of IKZF2 and miR-4772-3p were measured using quantitative real-time reverse transcription polymerase chain reaction. The interaction between miR-4772-3p and Helios was determined using dual-luciferase reporter assays. The effects of miR-4772-3p on Helios expression were evaluated using an in vitro system. Correlation assays between miR-4772-3p and functional molecules of Tregs were performed.
Results:Compared with non-malignant controls, patients with non-small cell lung cancer had an increased Tregs frequency with Helios expression in the MPE and peripheral blood mononuclear cells. The verified downregulation of miR-4772-3p was inversely related to the Helios+ Tregs frequency and Helios expression in the MPE. Overexpression of miR-4772-3p could inhibit Helios expression in in vitro experiments. However, ectopic expression of Helios in induced Tregs reversed the effects induced by miR-4772-3p overexpression. Additionally, miR-4772-3p could regulate Helios expression by directly targeting IKZF2 mRNA.
Conclusion:Downregulation of miR-4772-3p, by targeting Helios, contributes to enhanced Tregs activities in the MPE microenvironment.
