miR-21 regulates immunosuppression mediated by myeloid-derived suppressor cells by impairing RUNX1-YAP interaction in lu
- PDF / 1,831,217 Bytes
- 16 Pages / 595.276 x 790.866 pts Page_size
- 63 Downloads / 177 Views
Cancer Cell International Open Access
PRIMARY RESEARCH
miR‑21 regulates immunosuppression mediated by myeloid‑derived suppressor cells by impairing RUNX1‑YAP interaction in lung cancer Guangping Meng1, Jinying Wei1,2, Yanjun Wang3, Danhua Qu1 and Jie Zhang1*
Abstract Background: Myeloid-derived suppressor cells (MDSCs) are known suppressors of antitumor immunity and contribute to immunosuppressive microenvironment during tumor development including lung cancer. Accumulating evidence shows microRNAs (miRNAs) affect tumor-expanded MDSC accumulation and function in tumor microenvironment and favor solid tumor growth. Herein, we aim to characterize the role of miR-21 in regulating the accumulation and activity of MDSCs in lung cancer. Methods: The proportions of MDSCs, T helper cells (Th), and cytotoxic T lymphocytes (CTL) were evaluated by flow cytometric analyses of peripheral blood and tumor tissues collected from Lewis lung-cancer-bearing mice. T cell proliferation assay was performed in CD4+ or CD8+ T cells cocultured with MDSCs. MDSC apoptosis was examined by flow cytometric analysis. The levels of IL-10, TGF-β, and GM-CSF in mouse serum were determined by ELISA. miR21 targeting RUNX1 and RUNX1 interaction with YAP were evaluated by RIP, dual-luciferase reporter gene, and ChIP assays. Results: MiR-21 inhibition by its antagomir reduced the proportion of MDSCs, increased the proportion of Th and CTL in peripheral blood and tumor tissues of Lewis lung-cancer-bearing mice, protected Th and CTL from the suppression of MDSCs, increased apoptosis of MDSCs, but reduced IL-10, TGF-β and GM-CSF levels in mouse serum. RUNX1 could transcriptionally inhibit the YAP expression, whereas miR-21 targeting RUNX1 led to elevated YAP expression levels. Mechanistic investigation showed that miR-21 maintained MDSC accumulation in tumor microenvironment and promoted immunosuppressive ability of MDSCs in Lewis lung-cancer-bearing mice by down-regulating RUNX1and up-regulating YAP. Conclusions: Taken together, the study provides evidence that targeting miR-21 in MDSCs may be developed as an immunotherapeutic approach to combat lung cancer development. Keywords: Lung cancer, microRNA-21, Runt-related transcription factor 1, Yes-associated Protein, Myeloid-derived suppressor cells, Immunosuppressive ability
*Correspondence: [email protected] 1 Department of Respiratory and Critical Care Medicine, The Second Hospital of Jilin University, No. 218, Ziqiang Street, Changchun 130000, Jilin, People’s Republic of China Full list of author information is available at the end of the article
Background Lung cancer is one of the widely-diagnosed cancers around the world, and remains one of the leading causes of cancer-associated mortality in both men and women [1]. Moreover, less than 7% of patients survive 10 years
© The Author(s) 2020. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give
Data Loading...
