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

التفاصيل البيبلوغرافية
العنوان: microRNA-128-3p inhibits CD4+ regulatory T cells enrichment by targeting interleukin 16 in gastric cancer
المؤلفون: Weidan Fang, Chao Shi, Yiting Wang, Jianping Song, Ling Zhang
المصدر: Bioengineered, Vol 13, Iss 1, Pp 1025-1038 (2022)
Bioengineered
article-version (VoR) Version of Record
بيانات النشر: Taylor & Francis Group, 2022.
سنة النشر: 2022
مصطلحات موضوعية: CD4-Positive T-Lymphocytes, Interleukin-16, gastric cancer, Bioengineering, General Medicine, Prognosis, Applied Microbiology and Biotechnology, Survival Analysis, Coculture Techniques, cd4+ regulatory t cells, Up-Regulation, Gene Expression Regulation, Neoplastic, MicroRNAs, HEK293 Cells, Stomach Neoplasms, Cell Line, Tumor, microrna-128-3p, tumor-infiltrating lymphocytes, Humans, 3' Untranslated Regions, interleukin 16, TP248.13-248.65, Research Article, Research Paper, Biotechnology
الوصف: 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.
اللغة: English
تدمد: 2165-5987
2165-5979
URL الوصول: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::09efdce966c95a24a4c81a2984f72395
https://doaj.org/article/a46cf412a13c4508a68d786d06b0a936
حقوق: OPEN
رقم الأكسشن: edsair.doi.dedup.....09efdce966c95a24a4c81a2984f72395
قاعدة البيانات: OpenAIRE