microRNA-128-3p inhibits CD4+ regulatory T cells enrichment by targeting interleukin 16 in gastric cancer.
microRNA-128-3p inhibits CD4+ regulatory T cells enrichment by targeting interleukin 16 in gastric cancer.
复制标题
microRNA-128-3p 通过靶向胃癌中的白细胞介素 16 抑制 CD4 调节性 T 细胞富集
DOI：
10.1080/21655979.2021.2017566
复制
发表时间：
2022-01
期刊：
影响因子：
4.9
通讯作者：
Zhang L
中科院分区：
文献类型：
--
作者：
Fang W;Shi C;Wang Y;Song J;Zhang L
摘要已有研究证实microRNA（miR）-128-3p在胃癌中低水平表达，miR-128- 3 p的低表达促进胃癌细胞的生长。然而，miR-128- 3 p表达的失调是否会影响肿瘤浸润淋巴细胞（TIL）并导致免疫逃逸仍不清楚。在本研究中，预测性生物信息学方法显示，miR-128- 3 p表达与肿瘤浸润淋巴细胞富集呈负相关。当CD 4 + T细胞和调节性T细胞（Tcells）富集时，较低的miR-128- 3 p表达与较差的总生存期相关。然而，当CD 8 + T细胞数量减少时，miR-128- 3 p表达的上调对GC预后具有有利影响。双荧光素酶报告基因分析和细胞生物学实验表明，白细胞介素16（IL 16）是miR-128- 3 p的靶点，并受到miR-128- 3 p的负调控。此外，将胃癌细胞与T淋巴细胞共培养，随后的流式细胞术分析显示，肿瘤细胞中miR-128- 3 p的过表达通过下调胃癌中IL 16的表达来降低CD 4 + CD 25 + Foxp 3 + T淋巴细胞的百分比，而miR-128- 3 p的抑制则具有相反的效果。此外，重组IL 16逆转了miR-128- 3 p过表达的作用，并且针对IL 16受体CD 4的竞争性抗体也逆转了miR-128- 3 p敲低的作用。这些研究确定了miR-128- 3 p/IL 16轴促进GC中CD 4 + T细胞浸润的机制，该机制将成为GC免疫治疗中有希望的治疗靶点。
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.
登录
查看更多内容
影响因子：
4.4
作者：
McFadden, Caroline;Morgan, Ross;Cruikshank, William
通讯作者：
Cruikshank, William
影响因子：
3.7
作者：
Lee HM;Nguyen DT;Lu LF
通讯作者：
Lu LF
miR-128 通过靶向 p38 增强树突状细胞介导的抗肿瘤免疫
影响因子：
3.4
作者：
Liang X;Shangguan W;Zhang M;Mei S;Wang L;Yang R
通讯作者：
Yang R
DOI：
10.1042/cs20200573
发表时间：
2021-01-29
期刊：
Clinical science (London, England : 1979)
影响因子：
--
作者：
Gao M;Yu T;Liu D;Shi Y;Yang P;Zhang J;Wang J;Liu Y;Zhang X
通讯作者：
Zhang X
影响因子：
4.7
作者：
Gao, Lin-Bo;Rao, Li;Zhang, Lin
通讯作者：
Zhang, Lin