The Potential Role of IL1RAP on Tumor Microenvironment-Related Inflammatory Factors in Stomach Adenocarcinoma

Overview

Journal Technol Cancer Res Treat

Specialties Biomedical Engineering
Oncology
Pharmacology

Date 2021 Feb 19

PMID 33602046

Citations 11

Authors

Qing Lv

Qinghua Xia

Anshu Li

Zhiyong Wang

Affiliations

Soon will be listed here.

Abstract

This study was performed to investigate the role of interleukin-1 receptor accessory protein (IL1RAP) in stomach carcinoma in vitro and in vivo, determine whether IL1RAP knockdown could regulate the development of stomach carcinoma, and elucidate the relationship between IL1RAP knockdown and inflammation by tumor microenvironment-related inflammatory factors in stomach carcinoma. We first used TCGA and GEPIA systems to predict the potential function of IL1RAP. Second, western blot and RT-PCR were used to analyze the expression, or mRNA level, of IL1RAP at different tissue or cell lines. Third, the occurrence and development of stomach carcinoma in vitro and in vivo were observed by using IL1RAP knockdown lentivirus. Finally, the inflammation of stomach carcinoma in vitro and in vivo was observed. Results show that in GEPIA and TCGA systems, IL1RAP expression in STAD tumor tissue was higher than normal, and high expression of IL1RAP in STAD patients had a worse prognostic outcome. Besides, GSEA shown IL1RAP was negative correlation of apopopsis, TLR4 and NF-κB signaling pathway. We also predicted that IL1RAP may related to IL-1 s, IL-33, and IL-36 s in STAD. The IL1RAP expression and mRNA level in tumor, or MGC803, cells were increased. Furthermore, IL1RAP knockdown by lentivirus could inhibit stomach carcinoma development in vitro and in vivo through weakening tumor cell proliferation, migration, invasion, therefore reducing tumor volume, weight, and biomarker levels, and increasing apoptotic level. Finally, we found IL1RAP knockdown could increase inflammation of tumor microenvironment-related inflammatory factors of stomach carcinoma, in vitro and in vivo. Our study demonstrates that IL1RAP is possibly able to regulate inflammation and apoptosis in stomach carcinoma. Furthermore, TLR4, NF-κB, IL-1 s, IL-33, and IL-36 s maybe the downstream target factor of IL1RAP in inflammation. These results may provide a new strategy for stomach carcinoma development by regulating inflammation.

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References

He J, Li X, Zhu W, Yu Y, Gong J . Research of differential expression of sIL1RAP in low-grade gliomas between children and adults. Brain Tumor Pathol. 2017; 35(1):19-28. DOI: 10.1007/s10014-017-0304-x. View

Cikutovic-Molina R, Herrada A, Gonzalez W, Brown N, Zuniga L . Gene Knockdown Dampens Invasion and Migration and Promotes Apoptosis in KATO III and MKN-45 Human Gastric Adenocarcinoma Cell Lines. Int J Mol Sci. 2019; 20(23). PMC: 6928893. DOI: 10.3390/ijms20236077. View

Hong J, Son D, Lee C, Yoon D, Lee D, Park M . Interleukin 32, inflammation and cancer. Pharmacol Ther. 2017; 174:127-137. DOI: 10.1016/j.pharmthera.2017.02.025. View

Chen G, Xu M, Chen J, Hong L, Lin W, Zhao S . Clinicopathological Features and Increased Expression of Toll-Like Receptor 4 of Gastric Cardia Cancer in a High-Risk Chinese Population. J Immunol Res. 2018; 2018:7132868. PMC: 5835293. DOI: 10.1155/2018/7132868. View

Chen R, Li M, Zhang Y, Zhou Q, Shu H . The E3 ubiquitin ligase MARCH8 negatively regulates IL-1β-induced NF-κB activation by targeting the IL1RAP coreceptor for ubiquitination and degradation. Proc Natl Acad Sci U S A. 2012; 109(35):14128-33. PMC: 3435212. DOI: 10.1073/pnas.1205246109. View

ONeill L . The interleukin-1 receptor/Toll-like receptor superfamily: 10 years of progress. Immunol Rev. 2009; 226:10-8. DOI: 10.1111/j.1600-065X.2008.00701.x. View

Hu H, Ai X, Lu M, Song Z, Li H . Characterization of intratumoral and circulating IL-10-producing B cells in gastric cancer. Exp Cell Res. 2019; 384(2):111652. DOI: 10.1016/j.yexcr.2019.111652. View

Wang M, Busuttil R, Pattison S, Neeson P, Boussioutas A . Immunological battlefield in gastric cancer and role of immunotherapies. World J Gastroenterol. 2016; 22(28):6373-84. PMC: 4968119. DOI: 10.3748/wjg.v22.i28.6373. View

Mantovani A, Barajon I, Garlanda C . IL-1 and IL-1 regulatory pathways in cancer progression and therapy. Immunol Rev. 2017; 281(1):57-61. PMC: 5922413. DOI: 10.1111/imr.12614. View

10.

Falkesgaard Hojen J, Kristensen M, McKee A, Wade M, Azam T, Lunding L . IL-1R3 blockade broadly attenuates the functions of six members of the IL-1 family, revealing their contribution to models of disease. Nat Immunol. 2019; 20(9):1138-1149. PMC: 6707854. DOI: 10.1038/s41590-019-0467-1. View

11.

Warda W, Larosa F, Neto Da Rocha M, Trad R, Deconinck E, Fajloun Z . CML Hematopoietic Stem Cells Expressing IL1RAP Can Be Targeted by Chimeric Antigen Receptor-Engineered T Cells. Cancer Res. 2018; 79(3):663-675. DOI: 10.1158/0008-5472.CAN-18-1078. View

12.

Smallridge R, Chindris A, Asmann Y, Casler J, Serie D, Reddi H . RNA sequencing identifies multiple fusion transcripts, differentially expressed genes, and reduced expression of immune function genes in BRAF (V600E) mutant vs BRAF wild-type papillary thyroid carcinoma. J Clin Endocrinol Metab. 2013; 99(2):E338-47. PMC: 3913813. DOI: 10.1210/jc.2013-2792. View

13.

Backert S, Naumann M . What a disorder: proinflammatory signaling pathways induced by Helicobacter pylori. Trends Microbiol. 2010; 18(11):479-86. DOI: 10.1016/j.tim.2010.08.003. View

14.

Mitchell K, Barreyro L, Todorova T, Taylor S, Antony-Debre I, Narayanagari S . IL1RAP potentiates multiple oncogenic signaling pathways in AML. J Exp Med. 2018; 215(6):1709-1727. PMC: 5987926. DOI: 10.1084/jem.20180147. View

15.

Fan L, Tan B, Li Y, Zhao Q, Yuan H, Liu Y . Upregulation of miR‑185 promotes apoptosis of the human gastric cancer cell line MGC803. Mol Med Rep. 2017; 17(2):3115-3122. DOI: 10.3892/mmr.2017.8206. View

16.

de Martel C, Forman D, Plummer M . Gastric cancer: epidemiology and risk factors. Gastroenterol Clin North Am. 2013; 42(2):219-40. DOI: 10.1016/j.gtc.2013.01.003. View

17.

Xiang T, Jiang H, Zhang B, Liu G . CircFOXO3 functions as a molecular sponge for miR-143-3p to promote the progression of gastric carcinoma via upregulating USP44. Gene. 2020; 753:144798. DOI: 10.1016/j.gene.2020.144798. View

18.

Halbrook C, Lyssiotis C . Employing Metabolism to Improve the Diagnosis and Treatment of Pancreatic Cancer. Cancer Cell. 2017; 31(1):5-19. DOI: 10.1016/j.ccell.2016.12.006. View

19.

Serizawa T, Hirata Y, Hayakawa Y, Suzuki N, Sakitani K, Hikiba Y . Gastric Metaplasia Induced by Helicobacter pylori Is Associated with Enhanced SOX9 Expression via Interleukin-1 Signaling. Infect Immun. 2015; 84(2):562-72. PMC: 4730566. DOI: 10.1128/IAI.01437-15. View

20.

Waldum H, Fossmark R . Types of Gastric Carcinomas. Int J Mol Sci. 2018; 19(12). PMC: 6321162. DOI: 10.3390/ijms19124109. View