LPS‑induced downregulation of microRNA‑204/211 upregulates and stabilizes Angiopoietin‑1 mRNA in EA.hy926 endothelial cells

Zhang,Yijun; Gan,Caixia; Zhang,Jiangbo; Chen,Dong

doi:10.3892/mmr.2017.7400

LPS‑induced downregulation of microRNA‑204/211 upregulates and stabilizes Angiopoietin‑1 mRNA in EA.hy926 endothelial cells

Authors:
- Yijun Zhang
- Caixia Gan
- Jiangbo Zhang
- Dong Chen
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Affiliations: Sun Yat‑sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, Guangdong 510060, P.R. China
Published online on: August 30, 2017 https://doi.org/10.3892/mmr.2017.7400
Pages: 6081-6087
Copyright: © Zhang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Angiopoietin‑1 (ANG‑1), a ligand of the endothelial cell‑specific TIE2 surface receptor, acts in a complementary and coordinated manner with vascular endothelial growth factor during the process of angiogenesis. ANG‑1 can be used as a clinically informative biomarker of disease severity and outcome in severe sepsis. The epithelium‑specific Ets transcription factor 1 can activate ANG‑1 transcription in the setting of inflammation; however, relatively little is known about the regulation of ANG‑1 by microRNAs (miRs). It was observed that lipopolysaccharide (LPS) significantly increased ANG‑1 mRNA and protein expression in EA.hy926 cells. ANG‑1 was identified as a potential target gene of miR‑204 and miR‑211. Overexpression of miR‑204/211 partially reversed the LPS‑induced ANG‑1 expression in EA.hy926 cells. Furthermore, overexpression of miR‑204/211 significantly reduced the activity of a luciferase reporter gene containing the wild‑type ANG‑1 3'‑untranslated region (UTR), but did not influence the activity of a luciferase reporter gene containing the ANG‑1 3'‑UTR with a mutated miR‑204/211 binding site, confirming that miR‑204/211 can bind to the ANG‑1 3'‑UTR and post‑transcriptionally regulate ANG‑1. Additionally, LPS enhanced the stability of ANG‑1 mRNA by reducing the abundance of miR‑204/211. Overexpression of miR‑204/211 reduced the migration of EA.hy926 cells in vitro. The present study demonstrated that ANG‑1 is a novel direct target gene of miR‑204 and miR‑211; in addition, LPS was able to inhibit this effect by reducing the expression of miR‑204 and miR‑211.

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1	Hansen TM, Singh H, Tahir TA and Brindle NP: Effects of angiopoietins-1 and −2 on the receptor tyrosine kinase tie2 are differentially regulated at the endothelial cell surface. Cell Signal. 22:527–532. 2010. View Article : Google Scholar : PubMed/NCBI
2	Augustin HG, Koh GY, Thurston G and Alitalo K: Control of vascular morphogenesis and homeostasis through the angiopoietin-tie system. Nat Rev Mol Cell Biol. 10:165–177. 2009. View Article : Google Scholar : PubMed/NCBI
3	Chen L, Li J, Wang F, Dai C, Wu F, Liu X, Li T, Glauben R, Zhang Y, Nie G, et al: Tie2 expression on macrophages is required for blood vessel reconstruction and tumor relapse after chemotherapy. Cancer Res. 76:6828–6838. 2016. View Article : Google Scholar : PubMed/NCBI
4	Erber R, Thurnher A, Katsen AD, Groth G, Kerger H, Hammes HP, Menger MD, Ullrich A and Vajkoczy P: Combined inhibition of VEGF and PDGF signaling enforces tumor vessel regression by interfering with pericyte-mediated endothelial cell survival mechanisms. FASEB J. 18:338–340. 2004.PubMed/NCBI
5	Jackson KA, Majka SM, Wang H, Pocius J, Hartley CJ, Majesky MW, Entman ML, Michael LH, Hirschi KK and Goodell MA: Regeneration of ischemic cardiac muscle and vascular endothelium by adult stem cells. J Clin Invest. 107:1395–1402. 2001. View Article : Google Scholar : PubMed/NCBI
6	Chen L, Endler A, Uchida K, Horiguchi S, Morizane Y, Iijima O, Toi M and Shibasaki F: Int6/eif3e silencing promotes functional blood vessel outgrowth and enhances wound healing by upregulating hypoxia-induced factor 2alpha expression. Circulation. 122:910–919. 2010. View Article : Google Scholar : PubMed/NCBI
7	Abdel-Malak NA, Mofarrahi M, Mayaki D, Khachigian LM and Hussain SN: Early growth response-1 regulates angiopoietin-1-induced endothelial cell proliferation, migration, and differentiation. Arterioscler Thromb Vasc Biol. 29:209–216. 2009. View Article : Google Scholar : PubMed/NCBI
8	Clavel G, Bessis N, Lemeiter D, Fardellone P, Mejjad O, Ménard JF, Pouplin S, Boumier P, Vittecoq O, Le Loët X and Boissier MC: Angiogenesis markers (VEGF, soluble receptor of VEGF and angiopoietin-1) in very early arthritis and their association with inflammation and joint destruction. Clin Immunol. 124:158–164. 2007. View Article : Google Scholar : PubMed/NCBI
9	Chan W, Ismail H, Mayaki D, Sanchez V, Tiedemann K, Davis EC and Hussain SN: Fibulin-5 regulates angiopoietin-1/tie-2 receptor signaling in endothelial cells. PLoS One. 11:e01569942016. View Article : Google Scholar : PubMed/NCBI
10	Conroy AL, Phiri H, Hawkes M, Glover S, Mallewa M, Seydel KB, Taylor TE, Molyneux ME and Kain KC: Endothelium-based biomarkers are associated with cerebral malaria in malawian children: A retrospective case-control study. PLoS One. 5:e152912010. View Article : Google Scholar : PubMed/NCBI
11	Paulus P, Jennewein C and Zacharowski K: Biomarkers of endothelial dysfunction: Can they help us deciphering systemic inflammation and sepsis? Biomarkers. 16 Suppl 1:S11–S21. 2011. View Article : Google Scholar : PubMed/NCBI
12	Ben-Av P, Crofford LJ, Wilder RL and Hla T: Induction of vascular endothelial growth factor expression in synovial fibroblasts by prostaglandin e and interleukin-1: A potential mechanism for inflammatory angiogenesis. FEBS Lett. 372:83–87. 1995. View Article : Google Scholar : PubMed/NCBI
13	Paleolog EM, Young S, Stark AC, McCloskey RV, Feldmann M and Maini RN: Modulation of angiogenic vascular endothelial growth factor by tumor necrosis factor alpha and interleukin-1 in rheumatoid arthritis. Arthritis Rheum. 41:1258–1265. 1998. View Article : Google Scholar : PubMed/NCBI
14	Brown C, Gaspar J, Pettit A, Lee R, Gu X, Wang H, Manning C, Voland C, Goldring SR, Goldring MB, et al: Ese-1 is a novel transcriptional mediator of angiopoietin-1 expression in the setting of inflammation. J Biol Chem. 279:12794–12803. 2004. View Article : Google Scholar : PubMed/NCBI
15	Lu M, Zhang Q, Deng M, Miao J, Guo Y, Gao W and Cui Q: An analysis of human microRNA and disease associations. PLoS One. 3:e34202008. View Article : Google Scholar : PubMed/NCBI
16	Khabar KS: Post-transcriptional control during chronic inflammation and cancer: A focus on AU-rich elements. Cell Mol Life Sci. 67:2937–2955. 2010. View Article : Google Scholar : PubMed/NCBI
17	Chen J, Yang T, Yu H, Sun K, Shi Y, Song W, Bai Y, Wang X, Lou K, Song Y, et al: A functional variant in the 3′-UTR of angiopoietin-1 might reduce stroke risk by interfering with the binding efficiency of microRNA 211. Hum Mol Genet. 19:2524–2533. 2010. View Article : Google Scholar : PubMed/NCBI
18	Edgell CJ, McDonald CC and Graham JB: Permanent cell line expressing human factor VIII-related antigen established by hybridization. Proc Natl Acad Sci USA. 80:3734–3737. 1983; View Article : Google Scholar : PubMed/NCBI
19	Kitamura T, Koshino Y, Shibata F, Oki T, Nakajima H, Nosaka T and Kumagai H: Retrovirus-mediated gene transfer and expression cloning: Powerful tools in functional genomics. Exp Hematol. 31:1007–1014. 2003. View Article : Google Scholar : PubMed/NCBI
20	Huang J, Zhao L, Xing L and Chen D: MicroRNA-204 regulates Runx2 protein expression and mesenchymal progenitor cell differentiation. Stem Cells. 28:357–364. 2010.PubMed/NCBI
21	Qin J, Chen X, Xie X, Tsai MJ and Tsai SY: COUP-TFII regulates tumor growth and metastasis by modulating tumor angiogenesis. Proc Natl Acad Sci USA. 107:3687–3692. 2010; View Article : Google Scholar : PubMed/NCBI
22	Mofarrahi M, Nouh T, Qureshi S, Guillot L, Mayaki D and Hussain SN: Regulation of angiopoietin expression by bacterial lipopolysaccharide. Am J Physiol Lung Cell Mol Physiol. 294:L955–L963. 2008. View Article : Google Scholar : PubMed/NCBI
23	Bodolay E, Koch AE, Kim J, Szegedi G and Szekanecz Z: Angiogenesis and chemokines in rheumatoid arthritis and other systemic inflammatory rheumatic diseases. J Cell Mol Med. 6:357–376. 2002. View Article : Google Scholar : PubMed/NCBI
24	Szekanecz Z, Pakozdi A, Szentpetery A, Besenyei T and Koch AE: Chemokines and angiogenesis in rheumatoid arthritis. Front Biosci (Elite Ed). 1:44–51. 2009.PubMed/NCBI
25	Santos IC, Silbiger VN, Higuchi DA, Gomes MA, Barcelos LS, Teixeira MM, Lopes MT, Cardoso VN, Lima MP, Araujo RC, et al: Angiostatic activity of human plasminogen fragments is highly dependent on glycosylation. Cancer Sci. 101:453–459. 2010. View Article : Google Scholar : PubMed/NCBI
26	Jackson JR, Bolognese B, Kircher CH, Marshall LA and Winkler JD: Modulation of angiogenesis in a model of chronic inflammation. Inflamm Res. 46 Suppl 2:S129–S130. 1997. View Article : Google Scholar : PubMed/NCBI
27	Papapetropoulos A, Fulton D, Mahboubi K, Kalb RG, O'Connor DS, Li F, Altieri DC and Sessa WC: Angiopoietin-1 inhibits endothelial cell apoptosis via the Akt/survivin pathway. J Biol Chem. 275:9102–9105. 2000. View Article : Google Scholar : PubMed/NCBI
28	Taganov KD, Boldin MP and Baltimore D: MicroRNAs and immunity: Tiny players in a big field. Immunity. 26:133–137. 2007. View Article : Google Scholar : PubMed/NCBI
29	O'Connell RM, Taganov KD, Boldin MP, Cheng G and Baltimore D: MicroRNA-155 is induced during the macrophage inflammatory response. Proc Natl Acad Sci USA. 104:1604–1609. 2007; View Article : Google Scholar : PubMed/NCBI
30	Lam EK, Wang X, Shin VY, Zhang S, Morrison H, Sun J, Ng EK, Yu J and Jin H: A microRNA contribution to aberrant Ras activation in gastric cancer. Am J Transl Res. 3:209–218. 2011.PubMed/NCBI
31	Wang FE, Zhang C, Maminishkis A, Dong L, Zhi C, Li R, Zhao J, Majerciak V, Gaur AB, Chen S and Miller SS: MicroRNA-204/211 alters epithelial physiology. FASEB J. 24:1552–1571. 2010. View Article : Google Scholar : PubMed/NCBI
32	Pioli PA, Weaver LK, Schaefer TM, Wright JA, Wira CR and Guyre PM: Lipopolysaccharide-induced IL-1 beta production by human uterine macrophages up-regulates uterine epithelial cell expression of human beta-defensin 2. J Immunol. 176:6647–6655. 2006. View Article : Google Scholar : PubMed/NCBI
33	Pedersen I and David M: MicroRNAs in the immune response. Cytokine. 43:391–394. 2008. View Article : Google Scholar : PubMed/NCBI
34	Jennewein C, von Knethen A, Schmid T and Brune B: MicroRNA-27b contributes to lipopolysaccharide-mediated peroxisome proliferator-activated receptor gamma (PPARgamma) mRNA destabilization. J Biol Chem. 285:11846–11853. 2010. View Article : Google Scholar : PubMed/NCBI