miRNA-20b inhibits cerebral ischemia-induced inflammation through targeting NLRP3

Zhao,Jingru; Wang,Hebo; Dong,Lipeng; Sun,Sujuan; Li,Litao

doi:10.3892/ijmm.2018.4043

miRNA-20b inhibits cerebral ischemia-induced inflammation through targeting NLRP3

Authors:
- Jingru Zhao
- Hebo Wang
- Lipeng Dong
- Sujuan Sun
- Litao Li
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Affiliations: Department of Neurology, Hebei General Hospital, Shijiazhuang, Hebei 050051, P.R. China
Published online on: December 31, 2018 https://doi.org/10.3892/ijmm.2018.4043
Pages: 1167-1178
Copyright: © Zhao et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

The present study was designed to investigate the role of microRNA (miRNA)‑20b in the inflammatory response during cerebral ischemia and the underlying mechanism following cerebral ischemia. A reverse transcription quantitative polymerase chain reaction assay was used to measure the expression of miRNA‑20b, and tumor necrosis factor α, interleukin (IL)‑6, IL‑18 and IL‑1β levels were measured using ELISA. In addition, the protein expression levels of NOD‑like receptor pyrin domain containing 3 (NLRP3), caspase‑1, IL‑1β and IL‑18 were determined by western blot analysis. It was determined that the expression of miRNA‑20b during cerebral ischemia was increased compared with the control group. The overexpression of miRNA‑20b increased the levels of IL‑1β and IL‑18 in the cerebral ischemia group through activation of the NLRP3 signaling pathway. Conversely, the downregulation of miRNA‑20b suppressed IL‑1β and IL‑18 levels in cerebral ischemia via suppression of the NLRP3 signaling pathway. Additionally, the overexpression of miRNA‑20b increased the levels of adenosine 5'‑triphosphate (ATP) and reactive oxygen species (ROS) in the cerebral ischemia group, which were decreased following the downregulation of miRNA‑20b. The inhibition of NLRP3 decreased the pro‑inflammatory effects of miRNA‑20b in cerebral ischemia. Suppression of ATP decreases the pro‑inflammatory effects of miRNA‑20b in cerebral ischemia. Suppression of ROS also decreases the pro‑inflammatory effects of miRNA‑20b in cerebral ischemia. Collectively, the present study provided novel insight into the role of miRNA‑20b upregulation in the promotion of inflammation following cerebral infarction, suggesting that the miRNA‑20b/NLRP3 axis may be a putative therapeutic target in cerebral ischemia.

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1	Kan H, Guo W, Huang Y and Liu D: MicroRNA-520g induces epithelial-mesenchymal transition and promotes metastasis of hepatocellular carcinoma by targeting SMAD7. FEBS Lett. 589:102–109. 2015. View Article : Google Scholar
2	Chao Y, Chung YH, Han G, Yoon JH, Yang J, Wang J, Shao GL, Kim BI and Lee TY: The combination of transcatheter arterial chemoembolization and sorafenib is well tolerated and effective in Asian patients with hepatocellular carcinoma: Final results of the START trial. Int J Cancer. 136:1458–1467. 2015. View Article : Google Scholar
3	Tao ZH, Wan JL, Zeng LY, Xie L, Sun HC, Qin LX, Wang L, Zhou J, Ren ZG, Li YX, et al: miR-612 suppresses the invasive-metastatic cascade in hepatocellular carcinoma. J Exp Med. 210:789–803. 2013. View Article : Google Scholar : PubMed/NCBI
4	Lv N, Kong Y, Mu L, Pan T, Xie Q and Zhao M: Effect of perioperative parecoxib sodium on postoperative pain control for transcatheter arterial chemoembolization for inoperable hepatocellular carcinoma: A prospective randomized trial. Eur Radiol. 26:3492–3499. 2016. View Article : Google Scholar : PubMed/NCBI
5	Chai R, Fu H, Zheng Z, Liu T, Ji S and Li G: Resveratrol inhibits proliferation and migration through SIRT1 mediated posttranslational modification of PI3K/AKT signaling in hepatocellular carcinoma cells. Mol Med Rep. 16:8037–8044. 2017. View Article : Google Scholar : PubMed/NCBI
6	Zhou SL, Zhou ZJ, Hu ZQ, Li X, Huang XW, Wang Z, Fan J, Dai Z and Zhou J: CXCR2/CXCL5 axis contributes to epithelial-mesenchymal transition of HCC cells through activating PI3K/Akt/GSK-3β/Snail signaling. Cancer Lett. 358:124–135. 2015. View Article : Google Scholar
7	Ito Y, Miyoshi E, Takeda T, Sakon M, Noda K, Tsujimoto M, Monden M, Taniguchi N and Matsuura N: Expression and possible role of ets-1 in hepatocellular carcinoma. Am J Clin Pathol. 114:719–725. 2000. View Article : Google Scholar : PubMed/NCBI
8	Miskiewicz A, Szparecki G, Durlik M, Rydzewska G, Ziobrowski I and Górska R: The Q705K and F359L single-nucleotide polymorphisms of NOD-like receptor signaling pathway: Association with chronic pancreatitis, pancreatic cancer, and periodontitis. Arch Immunol Ther Exp (Warsz). 63:485–494. 2015. View Article : Google Scholar
9	Castaño-Rodríguez N, Kaakoush NO, Goh KL, Fock KM and Mitchell HM: The NOD-like receptor signalling pathway in Helicobacter pylori infection and related gastric cancer: A case-control study and gene expression analyses. PLoS One. 9:e988992014. View Article : Google Scholar : PubMed/NCBI
10	Ungerbäck J, Belenki D, Jawad ul-Hassan A, Fredrikson M, Fransén K, Elander N, Verma D and Söderkvist P: Genetic variation and alterations of genes involved in NFkappaB/TNFAIP3- and NLRP3-inflammasome signaling affect susceptibility and outcome of colorectal cancer. Carcinogenesis. 33:2126–2134. 2012. View Article : Google Scholar
11	Pontillo A, Oshiro TM, Girardelli M, Kamada AJ, Crovella S and Duarte AJ: Polymorphisms in inflammasome' genes and susceptibility to HIV-1 infection. J Acquir Immune Defic Syndr. 59:121–125. 2012. View Article : Google Scholar : PubMed/NCBI
12	Cheng D, Zhang L, Yang G, Zhao L, Peng F, Tian Y, Xiao X, Chung RT and Gong G: Hepatitis C virus NS5A drives a PTEN-PI3K/Akt feedback loop to support cell survival. Liver Int. 35:1682–1691. 2015. View Article : Google Scholar
13	Wang XJ, Feng CW and Li M: ADAM17 mediates hypoxia-induced drug resistance in hepatocellular carcinoma cells through activation of EGFR/PI3K/Akt pathway. Mol Cell Biochem. 380:57–66. 2013. View Article : Google Scholar : PubMed/NCBI
14	Dong Y, Liang G, Yuan B, Yang C, Gao R and Zhou X: MALAT1 promotes the proliferation and metastasis of osteosarcoma cells by activating the PI3K/Akt pathway. Tumour Biol. 36:1477–1486. 2015. View Article : Google Scholar
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
16	Chen X, Yan L, Guo Z, Chen Y, Li M, Huang C, Chen Z and Meng X: Chenodeoxycholic acid attenuates high-fat diet-induced obesity and hyperglycemia via the G protein-coupled bile acid receptor 1 and proliferator-activated receptor gamma pathway. Exp Ther Med. 14:5305–5312. 2017.PubMed/NCBI
17	Bruusgaard A and Andersen RB: Chenodeoxycholic-acid treatments of rheumatoid arthritis. Lancet. 1:7001976. View Article : Google Scholar : PubMed/NCBI
18	Cao P, Feng F, Dong G, Yu C, Feng S, Song E, Shi G, Liang Y and Liang G: Estrogen receptor α enhances the transcriptional activity of ETS-1 and promotes the proliferation, migration and invasion of neuroblastoma cell in a ligand dependent manner. BMC Cancer. 15:4912015. View Article : Google Scholar
19	Ahmad A, Ginnebaugh KR, Sethi S, Chen W, Ali R, Mittal S and Sarkar FH: miR-20b is up-regulated in brain metastases from primary breast cancers. Oncotarget. 6:12188–12195. 2015. View Article : Google Scholar : PubMed/NCBI
20	Ozaki I, Mizuta T, Zhao G, Zhang H, Yoshimura T, Kawazoe S, Eguchi Y, Yasutake T, Hisatomi A, Sakai T and Yamamoto K: Induction of multiple matrix metalloproteinase genes in human hepatocellular carcinoma by hepatocyte growth factor via a transcription factor Ets-1. Hepatol Res. 27:289–301. 2003. View Article : Google Scholar : PubMed/NCBI
21	Mamori S and Tajiri H: Ets-1 is increased in anticancer drug-containing media and hypoxic cultures, similar to TACE. Scand J Gastroenterol. 44:507–508. 2009. View Article : Google Scholar
22	Ma H, Guo S, Luo Y, Wang Y, Wang H, He J, Tang J, Shen L and Song C: MicroRNA-20b promotes the accumulation of CD11b+Ly6G+Ly6C^low myeloid-derived suppressor cells in asthmatic mice. Cent Eur J Immunol. 42:30–38. 2017. View Article : Google Scholar :
23	Verma D, Bivik C, Farahani E, Synnerstad I, Fredrikson M, Enerbäck C, Rosdahl I and Söderkvist P: Inflammasome polymorphisms confer susceptibility to sporadic malignant melanoma. Pigment Cell Melanoma Res. 25:506–513. 2012. View Article : Google Scholar : PubMed/NCBI
24	Coskun M, Bjerrum JT, Seidelin JB, Troelsen JT, Olsen J and Nielsen OH: miR-20b, miR-98, miR-125b-1, and let-7e as new potential diagnostic biomarkers in ulcerative colitis. World J Gastroenterol. 19:4289–4299. 2013. View Article : Google Scholar : PubMed/NCBI
25	Girardelli M, Maestri I, Rinaldi RR, Tognon M, Boldorini R, Bovenzi M, Crovella S and Comar M: NLRP1 polymorphisms in patients with asbestos-associated mesothelioma. Infect Agent Cancer. 7:252012. View Article : Google Scholar : PubMed/NCBI
26	Pontillo A, Bricher P, Leal VN, Lima S, Souza PR and Crovella S: Role of inflammasome genetics in susceptibility to HPV infection and cervical cancer development. J Med Virol. 88:1646–1651. 2016. View Article : Google Scholar : PubMed/NCBI
27	Lou J, Wang Y, Zhang Z and Qiu W: MiR-20b inhibits mycobacterium tuberculosis induced inflammation in the lung of mice through targeting NLRP3. Exp Cell Res. 358:120–128. 2017. View Article : Google Scholar : PubMed/NCBI