Long noncoding RNA TCONS_00024652 regulates vascular endothelial cell proliferation and angiogenesis via microRNA‑21

Halimulati,Muertiza; Duman,Bagedati; Nijiat,Julaiti; Aizezi,Abudoureyimu

doi:10.3892/etm.2018.6594

Long noncoding RNA TCONS_00024652 regulates vascular endothelial cell proliferation and angiogenesis via microRNA‑21

Authors:
- Muertiza Halimulati
- Bagedati Duman
- Julaiti Nijiat
- Abudoureyimu Aizezi
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Affiliations: Department of Vascular and Thyroid Surgery, Center of Digestive and Vascular Surgery, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang 830054, P.R. China
Published online on: August 10, 2018 https://doi.org/10.3892/etm.2018.6594
Pages: 3309-3316
Copyright: © Halimulati et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Acute coronary syndrome caused by the rupture of atherosclerotic plaques is one of the primary causes of major cardiovascular events, and neovascularization within the plaque is closely associated with its stability. Long noncoding RNA (lncRNAs) is a type of noncoding RNA that serves a crucial role in regulating vascular endothelial cells (VECs). The aim of the present study was to investigate the effect of lncRNA TCONS_00024652 on the proliferation and angiogenesis of VECs following stimulation with TNF‑α. The expression of lncRNA and miRNA was measured in human umbilical vein endothelial cells (HUVECs) by reverse transcription‑quantitative polymerase chain reaction. Cell proliferation was measured using a Cell Counting Kit‑8 assay. Wound healing and tube formation assays were performed to determine cell migration and angiogenesis. Interactions between TCONS_00024652 and miR‑21 were determined using bioinformatics and a dual‑luciferase reporter assay. The results demonstrated that TCONS_00024652 is highly expressed in TNF‑α‑induced HUVECs. Functional assays demonstrated that the dysregulated expression of TCONS_00024652 promotes endothelial cell proliferation and angiogenesis, whereas TCONS_00024652 knockdown induces the opposite effects. Bioinformatics analysis using starBase predicted putative binding at the 3'‑untranslated region of TCONS_00024652 and miR‑21 and luciferase reporter assays further verified this interaction. The results of the present study suggest that the targeting of TCONS_00024652 by miR‑21 may be a potential method of improving vascular endothelial dysfunction, neovascularization maturation and plaque stabilization.

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1	Camaré C, Pucelle M, Nègre-Salvayre A and Salvayre R: Angiogenesis in the atherosclerotic plaque. Redox Biol. 12:18–34. 2017. View Article : Google Scholar : PubMed/NCBI
2	Weng J: Activation of CD137 signaling promotes angiogenesis in atherosclerosis via modulating endothelial Smad1/5-NFATc1 pathway. J Am Heart Assoc. 6:234–247. 2017. View Article : Google Scholar
3	Sun Z: Atherosclerosis and Atheroma Plaque Rupture: Imaging Modalities in the Visualization of Vasa Vasorum and Atherosclerotic Plaques. Sci World J. 23:1–12. 2014. View Article : Google Scholar
4	Mulligan-Kehoe MJ: The vasa vasorum in diseased and nondiseased arteries. Am J Physiol Heart Circ Physiol. 298:H295–H305. 2010. View Article : Google Scholar : PubMed/NCBI
5	Moguillansky D, Leng X, Carson A, Lavery L, Schwartz A, Chen X and Villanueva FS: Quantification of plaque neovascularization using contrast ultrasound: A histologic validation. Eur Heart J. 32:646–653. 2011. View Article : Google Scholar : PubMed/NCBI
6	Wu MY and Li CJ: New insights into the role of inflammation in the pathogenesis of atherosclerosis. Int J Mol Sci. 18:E20342017. View Article : Google Scholar : PubMed/NCBI
7	Pirillo A, Bonacina F, Norata GD and Catapano AL: The interplay of lipids, lipoproteins and immunity in atherosclerosis. Curr Atheroscler Rep. 20:122018. View Article : Google Scholar : PubMed/NCBI
8	Sedding DG, Boyle EC, Demandt JAF, Sluimer JC, Dutzmann J, Haverich A and Bauersachs J: Vasa vasorum angiogenesis: Key player in the initiation and progression of atherosclerosis and potential target for the treatment of cardiovascular disease. Front Immunol. 9:7062018. View Article : Google Scholar : PubMed/NCBI
9	Tsai MC, Manor O, Wan Y, Mosammaparast N, Wang JK, Lan F, Shi Y, Segal E and Chang HY: Long Noncoding RNA as modular scaffold of histone modification complexes. Science. 329:689–693. 2010. View Article : Google Scholar : PubMed/NCBI
10	Schmitz SU, Grote P and Herrmann BG: Mechanisms of long noncoding RNA function in development and disease. Cell Mol Life Sci. 73:2491–2509. 2016. View Article : Google Scholar : PubMed/NCBI
11	Taylor DH, Chu ETJ, Spektor R and Soloway PD: Long non-coding RNA regulation of reproduction and development. Mol Reprod Dev. 82:932–956. 2015. View Article : Google Scholar : PubMed/NCBI
12	Hecht PM, Ballesteros-Yanez I, Grepo N, Knowles JA and Campbell DB: Noncoding RNA in the transcriptional landscape of human neural progenitor cell differentiation. Front Neurosci. 9:3922015. View Article : Google Scholar : PubMed/NCBI
13	Wu G, Cai J, Han Y, Chen J, Huang ZP, Chen C, Cai Y, Huang H, Yang Y, Liu Y, et al: LincRNA-p21 regulates neointima formation, vascular smooth muscle cell proliferation, apoptosis and atherosclerosis by enhancing p53 activity. Circulation. 130:1452–1465. 2014. View Article : Google Scholar : PubMed/NCBI
14	Puthanveetil P, Chen S, Feng B, Gautam A and Chakrabarti S: Long non-coding RNA MALAT1 regulates hyperglycaemia induced inflammatory process in the endothelial cells. J Cell Mol Med. 19:1418–1425. 2015. View Article : Google Scholar : PubMed/NCBI
15	Leung A, Trac C, Jin W, Lanting L, Akbany A, Sætrom P, Schones DE and Natarajan R: Novel long non-coding RNAs are regulated by angiotensin II in vascular smooth muscle cells. Circ Res. 113:266–278. 2013. View Article : Google Scholar : PubMed/NCBI
16	Leisegang MS, Fork C, Josipovic I, Richter FM, Preussner J, Hu J, Miller MJ, Epah J, Hofmann P, Günther S, et al: Long noncoding RNA MANTIS facilitates endothelial angiogenic function. Circulation. 136:65–79. 2017. View Article : Google Scholar : PubMed/NCBI
17	Bhaskaran M and Mohan M: MicroRNAs: History, biogenesis and their evolving role in animal development and disease. Vet Pathol. 51:759–774. 2014. View Article : Google Scholar : PubMed/NCBI
18	Chen LJ, Lim SH, Yeh YT, Lien SC and Chiu JJ: Roles of microRNAs in atherosclerosis and restenosis. J Biomed Sci. 19:79–91. 2012. View Article : Google Scholar : PubMed/NCBI
19	Chistiakov DA, Sobenin IA, Orekhov AN and Bobryshev YV: Human miR-221/222 in physiological and atherosclerotic vascular remodeling. Biomed Res Int. 15:1216–1229. 2015.
20	Landskroner-Eiger S, Qiu C, Perrotta P, Siragusa M, Lee MY, Ulrich V, Luciano AK, Zhuang ZW, Corti F, Simons M, et al: Endothelial miR-17~92 cluster negatively regulates arteriogenesis via miRNA-19 repression of WNT signaling. Proc Natl Acad Sci USA. 112:12812–12817. 2015. View Article : Google Scholar : PubMed/NCBI
21	Haque R, Iuvone PM, He L, Choi KSC, Ngo A, Gokhale S, Aseem M and Park D: The MicroRNA-21 signaling pathway is involved in prorenin receptor (PRR)-induced VEGF expression in ARPE-19 cells under a hyperglycemic condition. Mol Vision. 23:251–262. 2017.
22	Luo M, Tan X, Mu L, Luo Y, Li R, Deng X, Chen N, Ren M, Li Y, Wang L, et al: MiRNA-21 mediates the antiangiogenic activity of metformin through targeting PTEN and SMAD7 expression and PI3K/AKT pathway. Sci Rep. 7:4521–4534. 2017.PubMed/NCBI
23	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
24	Li JH, Liu S, Zhou H, Qu LH and Yang JH: starBase v2.0: Decoding miRNA-ceRNA, miRNA-ncRNA and protein-RNA interaction networks from large-scale CLIP-Seq data. Nucleic Acids Res. 42:D92–D97. 2014. View Article : Google Scholar : PubMed/NCBI
25	Uchida S and Dimmeler S: Long noncoding RNAs in cardiovascular diseases. Circ Res. 116:737–750. 2015. View Article : Google Scholar : PubMed/NCBI
26	Zhang BY, Jin Z and Zhao Z: Long intergenic noncoding RNA 00305 sponges miR-136 to regulate the hypoxia induced apoptosis of vascular endothelial cells. Biomed Pharmacother. 94:238–243. 2017. View Article : Google Scholar : PubMed/NCBI
27	Li H, Zhu H and Ge J: Long noncoding RNA: Recent updates in atherosclerosis. Int J Biol Sci. 12:898–910. 2016. View Article : Google Scholar : PubMed/NCBI
28	Xu L, Wu Z, Chen Y, Zhu Q, Hamidi S and Navab R: MicroRNA-21 (miR-21) regulates cellular proliferation, invasion, migration and apoptosis by targeting PTEN, RECK and Bcl-2 in lung squamous carcinoma, Gejiu City, China. PLoS One. 9:5324–5337. 2014.
29	Sabatel C, Malvaux L, Bovy N, Deroanne C, Lambert V, Gonzalez ML, Colige A, Rakic JM, Noël A, Martial JA and Struman I: MicroRNA-21 exhibits antiangiogenic function by targeting rhob expression in endothelial cells. PLoS One. 6:6548–6560. 2011. View Article : Google Scholar
30	Osborn EA and Jaffer FA: Imaging inflammation and neovascularization in atherosclerosis: Clinical and translational molecular and structural imaging targets. Curr Opin Cardiol. 30:671–680. 2015. View Article : Google Scholar : PubMed/NCBI
31	De León H, Boué S, Schlage WK, Boukharov N, Westra JW, Gebel S, Van Hooser A, Talikka M, Fields RB, Veljkovic E, et al: A vascular biology network model focused on inflammatory processes to investigate atherogenesis and plaque instability. J Transl Med. 12:1852014. View Article : Google Scholar : PubMed/NCBI
32	Luo D, Luo Y, He Y, Zhang H, Zhang R, Li X, Dobrucki WL, Sinusas AJ, Sessa WC and Min W: Differential functions of tumor necrosis factor receptor 1 and 2 signaling in ischemia-mediated arteriogenesis and angiogenesis. Am J Pathol. 169:1886–1898. 2006. View Article : Google Scholar : PubMed/NCBI
33	Ulitsky I and Bartel DP: lincRNAs: Genomics, evolution and mechanisms. Cell. 154:26–46. 2013. View Article : Google Scholar : PubMed/NCBI
34	Di Gesualdo F, Capaccioli S and Lulli M: A pathophysiological view of the long non-coding RNA world. Oncotarget. 5:10976–10996. 2014. View Article : Google Scholar : PubMed/NCBI
35	Gomes CPC, Spencer H, Ford KL, Michel LYM, Baker AH, Emanueli C, Balligand JL and Devaux Y: Cardiolinc network: The function and therapeutic potential of long Non-coding RNAs in cardiovascular development and disease. Mol Ther Nucleic Acids. 8:494–507. 2017. View Article : Google Scholar : PubMed/NCBI
36	Boulberdaa M, Scott E, Ballantyne M, Garcia R, Descamps B, Angelini GD, Brittan M, Hunter A, McBride M, McClure J, et al: A role for the Long Noncoding RNA SENCR in commitment and function of endothelial cells. Mol Ther. 24:978–990. 2016. View Article : Google Scholar : PubMed/NCBI
37	Yan B, Yao J, Liu JY, Li XM, Wang XQ, Li YJ, Tao ZF, Song YC, Chen Q and Jiang Q: lncRNA-MIAT regulates microvascular dysfunction by functioning as a competing endogenous RNA. Circ Res. 116:1143–1156. 2015. View Article : Google Scholar : PubMed/NCBI
38	Li K, Blum Y, Verma A, Liu Z, Pramanik K, Leigh NR, Chun CZ, Samant GV, Zhao B, Garnaas MK, et al: A noncoding antisense RNA in tie-1 locus regulates tie-1 function in vivo. Blood. 115:133–139. 2010. View Article : Google Scholar : PubMed/NCBI
39	Lu W, Huang SY, Su L, Zhao BX and Miao JY: Long Noncoding RNA LOC100129973 suppresses apoptosis by targeting miR-4707-5p and miR-4767 in vascular endothelial cells. Sci Rep. 6:9533–9547. 2016.
40	Yang R, Li P, Zhang G, Lu C, Wang H and Zhao G: Long non-coding RNA XLOC_008466 functions as an oncogene in human non-small cell lung cancer by targeting miR-874. Cell Physiol Biochem. 42:126–136. 2017. View Article : Google Scholar : PubMed/NCBI
41	Cerezo AB, Hornedo-Ortega R, Alvarez-Fernandez MA, Troncoso AM and Garcia-Parrilla MC: Inhibition of VEGF-induced VEGFR-2 activation and HUVEC migration by melatonin and other bioactive indolic compounds. Nutrients. 9:E2492017. View Article : Google Scholar : PubMed/NCBI