VEGFR affects miR-3200-3p-mediated regulatory T cell senescence in tumour-derived exosomes in non-small cell lung cancer.

Autor: Hui K; Department of Oncology, The Affiliated Lianyungang Hospital of Xuzhou Medical University, No. 6 Zhenhua East Road, Lianyungang, 222061, Jiangsu, China., Dong C; Department of Oncology, The Affiliated Lianyungang Hospital of Xuzhou Medical University, No. 6 Zhenhua East Road, Lianyungang, 222061, Jiangsu, China., Hu C; Department of Oncology, The Affiliated Lianyungang Hospital of Xuzhou Medical University, No. 6 Zhenhua East Road, Lianyungang, 222061, Jiangsu, China., Li J; Department of Pharmacy, The Affiliated Lianyungang Hospital of Xuzhou Medical University, Lianyungang, Jiangsu, China., Yan D; Department of Oncology, The Affiliated Lianyungang Hospital of Xuzhou Medical University, No. 6 Zhenhua East Road, Lianyungang, 222061, Jiangsu, China., Jiang X; Department of Oncology, The Affiliated Lianyungang Hospital of Xuzhou Medical University, No. 6 Zhenhua East Road, Lianyungang, 222061, Jiangsu, China. jxdpaper@163.com.
Jazyk: angličtina
Zdroj: Functional & integrative genomics [Funct Integr Genomics] 2024 Feb 16; Vol. 24 (2), pp. 31. Date of Electronic Publication: 2024 Feb 16.
DOI: 10.1007/s10142-024-01305-2
Abstrakt: Numerous studies have demonstrated that regulatory T (Treg) cells play an important role in the tumour microenvironment (TME). The aim of this study was to investigate whether VEGFR2 affects the expression of miR-3200-3p in exosomes secreted by tumour cells, thereby influencing Treg senescence in the TME. The results showed that VEGFR2 expression level was the highest in Calu-1 cells, and after transfection with si-VEGFR2, the exosomes secreted from Calu-1 cells were extracted and characterised with no significant difference from the exosomes of the untransfected group, but the expression of miR-3200-3p in the exosomes of the transfected si-VEGFR2 group was elevated. The Cell Counting Kit-8 (CCK-8) and flow cytometry (FCM) results suggested that exosomes highly expressing miR-3200-3p could inhibit Treg cell viability and promote apoptosis levels when treated with Treg cells. Detection of the senescence-associated proteins p16 INK4A and MMP3 by western blot (WB) revealed that exosomes highly expressing miR-3200-3p were able to elevate their protein expression levels. Tumour xenograft experiments demonstrated that exosomes with high miR-3200-3p expression promoted Treg cell senescence and inhibited subcutaneous tumour growth in nude mice. Dual-luciferase reporter assays and RNA pull-down assays showed that miR-3200-3p could be linked with DDB1. Overexpression of DDB1 reverses changes in DCAF1/GSTP1/ROS protein expression caused by exosomes with high miR-3200-3p expression. In conclusion, inhibition of VEGFR2 expression in tumour cells promotes the expression of miR-3200-3p in exosomes secreted by tumour cells. miR-3200-3p enters the TME through exosomes and acts on DDB1 in Treg cells to promote senescence of Treg cells to inhibit tumour progression.
(© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)
Databáze: MEDLINE
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