Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.
ADVANCED SEARCH
Log in
Top
BMC Cancer
Published in: BMC Cancer 1/2018

Open Access 01-12-2018 | Research article

Long non-coding RNA RUNXOR accelerates MDSC-mediated immunosuppression in lung cancer

Authors: Xinyu Tian, Jie Ma, Ting Wang, Jie Tian, Yu Zheng, Rongrong Peng, Yungang Wang, Yue Zhang, Lingxiang Mao, Huaxi Xu, Shengjun Wang

Published in: BMC Cancer | Issue 1/2018

Login to get access

Abstract

Background

RUNX1 overlapping RNA (RUNXOR) is a long non-coding RNA that has been indicated as a key regulator in the development of myeloid cells by targeting runt-related transcription factor 1 (RUNX1). Myeloid-derived suppressor cells (MDSCs) are a heterogeneous population of cells consisting of immature granulocytes and monocytes with immunosuppression. However, the impact of lncRNA RUNXOR on the development of MDSCs remains unknown.

Methods

Both the expressions of RUNXOR and RUNX1 in the peripheral blood were measured by qRT-PCR. Human MDSCs used in this study were isolated from tumor tissue of patients with lung cancer by FCM or induced from PBMCs of healthy donors with IL-1β + GM-CSF. Specific siRNA was used to knockdown the expression of RUNXOR in MDSCs.

Results

In this study, we found that the lncRNA RUNXOR was upregulated in the peripheral blood of lung cancer patients. In addition, as a target gene of RUNXOR, the expression of RUNX1 was downregulated in lung cancer patients. Finally, the expression of RUNXOR was higher in MDSCs isolated from the tumor tissues of lung cancer patients compared with cells from adjacent tissue. In addition, RUNXOR knockdown decreased Arg1 expression in MDSCs.

Conclusions

Based on our findings, it is illustrated that RUNXOR is significantly associated with the immunosuppression induced by MDSCs in lung cancer patients and may be a target of anti-tumor therapy.
Literature
1.
Byron E, Pinder-Schenck M. Systemic and targeted therapies for early-stage lung cancer. Cancer control : journal of the Moffitt Cancer Center. 2014;21:21–31.CrossRef
2.
Kumar R, Collins D, Dolly S, McDonald F, O'Brien MER, Yap TA. Targeting the PD-1/PD-L1 axis in non-small cell lung cancer. Curr Probl Cancer. 2017;41:111–24.CrossRefPubMed
3.
Rafei H, El-Bahesh E, Finianos A, Nassereddine S, Tabbara I. Immune-based therapies for non-small cell lung cancer. Anticancer Res. 2017;37:377–87.CrossRefPubMed
4.
Ma J, Xu H, Wang S. Immunosuppressive role of myeloid-derived suppressor cells and therapeutic targeting in lung cancer. J Immunol Res. 2018;2018 6319649
5.
Shi G, Wang H, Zhuang X. Myeloid-derived suppressor cells enhance the expression of melanoma-associated antigen A4 in a Lewis lung cancer murine model. Oncol Lett. 2016;11(1):809–16.CrossRefPubMed
6.
Atretkhany KN, Drutskaya MS. Myeloid-derived suppressor cells and Proinflammatory cytokines as targets for Cancer therapy. Biochemistry Biokhimiia. 2016;81:1274–83.CrossRefPubMed
7.
Kumar V, Patel S, Tcyganov E, Gabrilovich DI. The nature of myeloid-derived suppressor cells in the tumor microenvironment. Trends Immunol. 2016;37:208–20.CrossRefPubMedPubMedCentral
8.
Lin Y, Yang X, Liu W, Li B, Yin W, Shi Y, et al. Chemerin has a protective role in hepatocellular carcinoma by inhibiting the expression of IL-6 and GM-CSF and MDSC accumulation. Oncogene. 2017;36:3599–608.CrossRefPubMed
9.
Youn JI, Collazo M, Shalova IN, Biswas SK, Gabrilovich DI. Characterization of the nature of granulocytic myeloid-derived suppressor cells in tumor-bearing mice. J Leukoc Biol. 2012;91:167–81.CrossRefPubMedPubMedCentral
10.
11.
Tian X, Tian J, Tang X, Rui K, Zhang Y, Ma J, et al. Particulate beta-glucan regulates the immunosuppression of granulocytic myeloid-derived suppressor cells by inhibiting NFIA expression. Oncoimmunology. 2015;4:e1038687.CrossRefPubMedPubMedCentral
12.
Tian J, Rui K, Tang X, Ma J, Wang Y, Tian X, et al. MicroRNA-9 regulates the differentiation and function of myeloid-derived suppressor cells via targeting Runx1. J Immunol. 2015;195:1301–11.CrossRefPubMed
13.
14.
Zeng C, Guo X, Long J, Kuchenbaecker KB, Droit A, Michailidou K. Identification of independent association signals and putative functional variants for breast cancer risk through fine-scale mapping of the 12p11 locus. Breast cancer research : BCR. 2016;18:64.CrossRefPubMedPubMedCentral
15.
Heward JA, Lindsay MA. Long non-coding RNAs in the regulation of the immune response. Trends Immunol. 2014;35:408–19.CrossRefPubMed
16.
17.
Wu T, Yin X, Zhou Y, Wang Z, Shen S, Qiu Y, et al. Roles of noncoding RNAs in metastasis of nonsmall cell lung cancer: a mini review. J Cancer Res Ther. 2015;11(Suppl 1):C7–10.PubMed
18.
Wan L, Sun M, Liu GJ, Wei CC, Zhang EB, Kong R, et al. Long noncoding RNA PVT1 promotes non-small cell lung cancer cell proliferation through epigenetically regulating LATS2 expression. Mol Cancer Ther. 2016;15:1082–94.CrossRefPubMed
19.
Peng H, Liu Y, Tian J, Ma J, Tang X, Rui K, et al. The long noncoding RNA IFNG-AS1 promotes T helper type 1 cells response in patients with Hashimoto's thyroiditis. Sci Rep. 2015;5:17702.CrossRefPubMedPubMedCentral
20.
Reddy MA, Chen Z, Park JT, Wang M, Lanting L, Zhang Q, et al. Regulation of inflammatory phenotype in macrophages by a diabetes-induced long noncoding RNA. Diabetes. 2014;63:4249–61.CrossRefPubMedPubMedCentral
21.
Wang H, Li W, Guo R, Sun J, Cui J, Wang G, et al. An intragenic long noncoding RNA interacts epigenetically with the RUNX1 promoter and enhancer chromatin DNA in hematopoietic malignancies. Int J Cancer. 2014;135:2783–94.CrossRefPubMed
22.
Pan T, Liu Y, Zhong LM, et al. Myeloid-derived suppressor cells are essential for maintaining feto-maternal immunotolerance via STAT3 signaling in mice. J Leukoc Biol. 2016;100:499–511.CrossRefPubMed
23.
Muthuswamy R, Corman JM, Dahl K, Chatta GS, Kalinski P. Functional reprogramming of human prostate cancer to promote local attraction of effector CD8(+) T cells. Prostate. 2016;76:1095–105.CrossRefPubMed
24.
Movahedi K, Guilliams M, Van den Bossche J, Van den Bergh R, Gysemans C, Beschin A, et al. Identification of discrete tumor-induced myeloid-derived suppressor cell subpopulations with distinct T cell-suppressive activity. Blood. 2008;111:4233–44.CrossRefPubMed
25.
Rodriguez PC, Ochoa AC. Arginine regulation by myeloid derived suppressor cells and tolerance in cancer: mechanisms and therapeutic perspectives. Immunol Rev. 2008;222:180–91.CrossRefPubMedPubMedCentral
26.
27.
Mandoli A, Singh AA, Prange KH, Tijchon E, Oerlemans M, Dirks R, et al. The hematopoietic transcription factors RUNX1 and ERG prevent AML1-ETO oncogene overexpression and onset of the apoptosis program in t(8;21) AMLs. Cell Rep. 2016;17:2087–100.CrossRefPubMed
28.
Paglia DN, Yang X, Kalinowski J, Jastrzebski S, Drissi H, Lorenzo J. Runx1 regulates myeloid precursor differentiation into osteoclasts without affecting differentiation into antigen presenting or phagocytic cells in both males and females. Endocrinology. 2016;157:3058–69.CrossRefPubMedPubMedCentral
29.
Wang J, Peng H, Tian J, Ma J, Tang X, Rui K, et al. Upregulation of long noncoding RNA TMEVPG1 enhances T helper type 1 cell response in patients with Sjögren syndrome. Immunol Res. 2016;64:489–696.CrossRefPubMed
30.
Wang Y, Yang T, Zhang Z, Lu M, Zhao W, Zeng X, et al. Long non-coding RNA TUG1 promotes migration and invasion by acting as a ceRNA of miR-335-5p in osteosarcoma cells. Cancer Sci. 2017;108:859–67.CrossRefPubMedPubMedCentral
31.
Tian X, Ma J, Wang T, Tian J, Zhang Y, Mao L, Xu H, Wang S. LncRNA HOTAIRM1-HOXA1 axis down-regulates the immunosuppressive activity of myeloid-derived suppressor cells in lung cancer. Front Immunol. 2018;9:473.CrossRefPubMedPubMedCentral
Metadata
Title
Long non-coding RNA RUNXOR accelerates MDSC-mediated immunosuppression in lung cancer
Authors
Xinyu Tian
Jie Ma
Ting Wang
Jie Tian
Yu Zheng
Rongrong Peng
Yungang Wang
Yue Zhang
Lingxiang Mao
Huaxi Xu
Shengjun Wang
Publication date
01-12-2018
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2018
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/s12885-018-4564-6

Other articles of this Issue 1/2018

BMC Cancer 1/2018 Go to the issue

Research article

Trastuzumab without chemotherapy in the adjuvant treatment of breast cancer: subgroup results from a large observational study

Research article

Effects of physical activity on colorectal cancer risk among family history and body mass index subgroups: a systematic review and meta-analysis

Research article

Low-dose aspirin use and survival in colorectal cancer: results from a population-based cohort study

Research article

B4GALT1 expression predicts prognosis and adjuvant chemotherapy benefits in muscle-invasive bladder cancer patients

Research article

Regulation of pancreatic stellate cell activation by Notch3

Research article

Extra-capsular growth of lymph node metastasis correlates with poor prognosis and high SOX9 expression in gastric cancer
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Watch now

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine
Image Credits