microRNA-128-3p inhibits CD4+ regulatory T cells enrichment by targeting interleukin 16 in gastric cancer.

Abstract

Previous studies have confirmed that microRNA (miR)-128-3p is expressed at low levels in gastric cancer (GC), and low miR-128-3p expression promotes the growth of GC cells. However, whether the dysregulation of miR-128-3p expression affects tumor-infiltrating lymphocytes (TILs) and leads to immune escape remains unclear. In the present study, predictive bioinformatics approaches showed that miR-128-3p expression was inversely correlated with tumor-infiltrating lymphocyte enrichment. When CD4 + T cells and regulatory T cells (Tregs) were enriched, lower miR-128-3p expression was associated with worse overall survival. However, when numbers of CD8 + T cells were decreased, the upregulation of miR-128-3p expression had a favorable effect on GC prognosis. Dual-luciferase reporter assays and cell biology experiments revealed that interleukin 16 (IL16) was the target of miR-128-3p and was negatively regulated by miR-128-3p. In addition, GC cells were cocultured with T lymphocytes, and the subsequent flow cytometric analysis showed that overexpression of miR-128-3p in tumor cells decreased the percentages of CD4+ CD25+ Foxp3+ Tregs by downregulating IL16 expression in GC, whereas miR-128-3p inhibition had the opposite effect. Moreover, the recombinant IL16 reversed the effects of miR-128-3p overexpression, and a competitive antibody against the IL16 receptor CD4 also reversed the effects of miR-128-3p knockdown. These studies identified the mechanism by which the miR-128-3p/IL16 axis promotes the infiltration of CD4+ Tregs in GC, and this mechanism will be a promising therapeutic target in GC immunotherapy.

• Authors: Weidan Fang, Chao Shi, Yiting Wang, Jianping Song, Ling Zhang
• Journal: Bioengineered (Bioengineered) Vol. 13 Issue 1 Pg. 1025-1038 (01 2022) ISSN: 2165-5987 [Electronic] United States
• PMID: 34968167 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• 3' Untranslated Regions
• Il16 protein, human
• Interleukin-16
• MIRN128 microRNA, human
• MicroRNAs

Topics

• 3' Untranslated Regions
• CD4-Positive T-Lymphocytes (metabolism)
• Cell Line, Tumor
• Coculture Techniques
• Gene Expression Regulation, Neoplastic
• HEK293 Cells
• Humans
• Interleukin-16 (genetics)
• MicroRNAs (genetics)
• Prognosis
• Stomach Neoplasms (genetics, immunology)
• Survival Analysis
• Up-Regulation