MicroRNA expression profiles of granulocytic myeloid‑derived suppressor cells from mice bearing Lewis lung carcinoma

Jiang,Jingwei; Gao,Qingmin; Wang,Tian; Lin,Hao; Zhan,Qiong; Chu,Zhaohui; Huang,Ruofan; Zhou,Xinli; Liang,Xiaohua; Guo,Weijian

doi:10.3892/mmr.2016.5845

MicroRNA expression profiles of granulocytic myeloid‑derived suppressor cells from mice bearing Lewis lung carcinoma

Authors:
- Jingwei Jiang
- Qingmin Gao
- Tian Wang
- Hao Lin
- Qiong Zhan
- Zhaohui Chu
- Ruofan Huang
- Xinli Zhou
- Xiaohua Liang
- Weijian Guo
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Affiliations: Department of Oncology, Huashan Hospital, Fudan University, Shanghai 200040, P.R. China, Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, P.R. China
Published online on: October 13, 2016 https://doi.org/10.3892/mmr.2016.5845
Pages: 4567-4574
Copyright: © Jiang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Myeloid-derived suppressor cells (MDSCs) are a group of heterogeneous myeloid cells that can suppress antitumor immunity. MDSCs are divided into granulocytic (G‑MDSCs) and monocytic subsets. In the present study, the microRNA profiles of the G‑MDSCs were determined and the differential expression of microRNAs between G‑MDSCs from tumor‑bearing mice and tumor‑free mice was examined. The number of G‑MDSCs in spleens of Lewis lung carcinoma (LLC)‑bearing mice was ~6‑fold higher than in spleens of normal mice (13.54±1.74% vs. 2.14±1.44%; P<0.01) and G‑MDSCs account for about 72.9% of all MDSCs. The microRNA (miRNA) profiles of the G‑MDSCs from spleen of LLC‑bearing mice were obtained using a microRNA microarray and compared with their counterparts from spleens of tumor‑free mice. A total of 43 miRNAs with >1.3‑fold increased or decreased change were differentially expressed between the experimental and control group mice. The levels of nine of these differentially expressed miRNAs, miRNA‑468 (miR‑486), miR‑192, miR‑128, miR‑125a, miR‑149, miR‑27a, miR‑125b, miR‑350 and miR‑328, were also analyzed by RT‑qPCR to validate the microarray data. The concordance rate between the results tested by the two methods was 88.9%. Bioinformatics analyses revealed that these miRNAs may act on various target genes, including Adar, Pik3r1, Rybp and Rabgap1, to regulate the survival, differentiation and the function of tumor‑induced granulocytic MDSCs. The results revealed microRNAs and potential targets that may be vital for regulating survival, differentiation and function of G‑MDSCs induced by LLC. Further investigation should be performed to clarify the roles of these microRNAs in regulating LLC‑induced granulocytic MDSCs and the target genes that mediate their functions.

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1	Gabrilovich DI and Nagaraj S: Myeloid-derived suppressor cells as regulators of the immune system. Nat Rev Immunol. 9:162–174. 2009. View Article : Google Scholar : PubMed/NCBI
2	Condamine T, Ramachandran I, Youn JI and Gabrilovich DI: Regulation of tumor metastasis by myeloid-derived suppressor cells. Annu Rev Med. 66:97–110. 2015. View Article : Google Scholar : PubMed/NCBI
3	Youn JI, Nagaraj S, Collazo M and Gabrilovich DI: Subsets of myeloid-derived suppressor cells in tumor-bearing mice. J Immunol. 181:5791–5802. 2008. View Article : Google Scholar : PubMed/NCBI
4	Movahedi K, Guilliams M, Van den Bossche J, Van den Bergh R, Gysemans C, Beschin A, De Baetselier P and Van Ginderachter JA: Identification of discrete tumor-induced myeloid-derived suppressor cell subpopulations with distinct T cell-suppressive activity. Blood. 111:4233–4244. 2008. View Article : Google Scholar : PubMed/NCBI
5	Lim HX, Hong HJ, Cho D and Kim TS: IL-18 enhances immunosuppressive responses by promoting differentiation into monocytic myeloid-derived suppressor cells. J Immunol. 193:5453–5460. 2014. View Article : Google Scholar : PubMed/NCBI
6	Medina-Echeverz J, Haile LA, Zhao F, Gamrekelashvili J, Ma C, Métais JY, Dunbar CE, Kapoor V, Manns MP, Korangy F and Greten TF: IFN-γ regulates survival and function of tumor-induced CD11b⁺ Gr⁻¹ high myeloid derived suppressor cells by modulating the anti-apoptotic molecule Bcl2a1. Eur J Immunol. 44:2457–2467. 2014. View Article : Google Scholar : PubMed/NCBI
7	O'Connell RM, Rao DS, Chaudhuri AA and Baltimore D: Physiological and pathological roles for microRNAs in the immune system. Nat Rev Immunol. 10:111–122. 2010. View Article : Google Scholar : PubMed/NCBI
8	Ekimler S and Sahin K: Computational methods for MicroRNA target prediction. Genes (Basel). 5:671–683. 2014.PubMed/NCBI
9	Jiang J, Guo W and Liang X: Phenotypes, accumulation, and functions of myeloid-derived suppressor cells and associated treatment strategies in cancer patients. Hum Immunol. 75:1128–1137. 2014. View Article : Google Scholar : PubMed/NCBI
10	Zhang M, Liu Q, Mi S, Liang X, Zhang Z, Su X, Liu J, Chen Y, Wang M, Zhang Y, et al: Both miR-17-5p and miR-20a alleviate suppressive potential of myeloid-derived suppressor cells by modulating STAT3 expression. J Immunol. 186:4716–4724. 2011. View Article : Google Scholar : PubMed/NCBI
11	Liu Y, Lai L, Chen Q, Song Y, Xu S, Ma F, Wang X, Wang J, Yu H, Cao X and Wang Q: MicroRNA-494 is required for the accumulation and functions of tumor-expanded myeloid-derived suppressor cells via targeting of PTEN. J Immunol. 188:5500–5510. 2012. View Article : Google Scholar : PubMed/NCBI
12	Li L, Zhang J, Diao W, Wang D, Wei Y, Zhang CY and Zen K: MicroRNA-155 and MicroRNA-21 promote the expansion of functional myeloid-derived suppressor cells. J Immunol. 192:1034–1043. 2014. View Article : Google Scholar : PubMed/NCBI
13	Wang X, Chang X, Zhuo G, Sun M and Yin K: Twist and miR-34a are involved in the generation of tumor-educated myeloid-derived suppressor cells. Int J Mol Sci. 14:20459–20477. 2013. View Article : Google Scholar : PubMed/NCBI
14	Huang A, Zhang H, Chen S, Xia F, Yang Y, Dong F, Sun D, Xiong S and Zhang J: miR-34a expands myeloid-derived suppressor cells via apoptosis inhibition. Exp Cell Res. 326:259–266. 2014. View Article : Google Scholar : PubMed/NCBI
15	Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(−Delta Delta C(T)) Method. Methods. 25:402–408. 2001. View Article : Google Scholar : PubMed/NCBI
16	Cline MS, Smoot M, Cerami E, Kuchinsky A, Landys N, Workman C, Christmas R, Avila-Campilo I, Creech M, Gross B, et al: Integration of biological networks and gene expression data using Cytoscape. Nat Protoc. 2:2366–2382. 2007. View Article : Google Scholar : PubMed/NCBI
17	Bindea G, Mlecnik B, Hackl H, Charoentong P, Tosolini M, Kirilovsky A, Fridman WH, Pagès F, Trajanoski Z and Galon J: ClueGO: A Cytoscape plug-in to decipher functionally grouped gene ontology and pathway annotation networks. Bioinformatics. 25:1091–1093. 2009. View Article : Google Scholar : PubMed/NCBI
18	Serafini P: Myeloid derived suppressor cells in physiological and pathological conditions: The good, the bad, and the ugly. Immunol Res. 57:172–184. 2013. View Article : Google Scholar : PubMed/NCBI
19	Trikha P and Carson WE III: Signaling pathways involved in MDSC regulation. Biochim Biophys Acta. 1846:55–65. 2014.PubMed/NCBI
20	Hukowska-Szematowicz B, Tokarz-Deptula B and Deptula W: MicroRNA (miRNA) and the immune system. Cent Eur J Immunol. 37:387–390. 2012. View Article : Google Scholar
21	Hauser B, Zhao Y, Pang X, Ling Z, Myers E, Wang P, Califano J and Gu X: Functions of miRNA-128 on the regulation of head and neck squamous cell carcinoma growth and apoptosis. PLoS One. 10:e01163212015. View Article : Google Scholar : PubMed/NCBI
22	La Torre A, Georgi S and Reh TA: Conserved microRNA pathway regulates developmental timing of retinal neurogenesis. Proc Natl Acad Sci USA. 110:E2362–E2370. 2013. View Article : Google Scholar : PubMed/NCBI