An integrated hypothesis for miR-126 in vascular disease
Main Article Content
Abstract
microRNA miR-126 was among the early discovered miRNAs that are expressed specifically in the vasculature and have critical functions in vascular development. Recent studies have started to unveil potentially important function of miR-126 in vascular diseases, including atherosclerosis, coronary artery disease, stroke and diabetic vasculopathy. The action of miR-126 reflects its function in angiogenesis and inflammation. The expression of miR-126 is downregulated in a variety of vascular diseases, and miR-126 overexpression appears to beneficial for most vascular disease models. In the minireview, we summarize the historic and current research regarding miR-126 function and mechanisms in the vascular system, its link to long noncoding RNAs (lncRNA), as well as the potential of miR-126-based therapeutics for vascular diseases. To explain the seemingly conflicting function of miR-126 from different studies, an integrated hypothesis is proposed that miR-126 has strand- and cell type-specific functions in angiogenesis and inflammation, making it beneficial in many different vascular disease models.
Article Details
How to Cite
YU, Bo et al.
An integrated hypothesis for miR-126 in vascular disease.
Medical Research Archives, [S.l.], v. 8, n. 5, may 2020.
ISSN 2375-1924.
Available at: <https://esmed.org/MRA/mra/article/view/2133>. Date accessed: 27 apr. 2024.
doi: https://doi.org/10.18103/mra.v8i5.2133.
Section
Research Articles
The Medical Research Archives grants authors the right to publish and reproduce the unrevised contribution in whole or in part at any time and in any form for any scholarly non-commercial purpose with the condition that all publications of the contribution include a full citation to the journal as published by the Medical Research Archives.
References
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11. Sun P, Liu DZ, Jickling GC, Sharp FR, Yin KJ. MicroRNA-based therapeutics in central nervous system injuries. J Cereb Blood Flow Metab. 2018;38(7):1125-1148.
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14. Wang JN, Yan YY, Guo ZY, Jiang YJ, Liu LL, Liu B. Negative Association of Circulating MicroRNA-126 with High-sensitive C-reactive Protein and Vascular Cell Adhesion Molecule-1 in Patients with Coronary Artery Disease Following Percutaneous Coronary Intervention. Chinese Med J-Peking. 2016;129(23):2786-2791.
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19. Wei XJ, Han M, Yang FY, et al. Biological significance of miR-126 expression in atrial fibrillation and heart failure. Braz J Med Biol Res. 2015;48(11):983-989.
20. Zampetaki A, Kiechl S, Drozdov I, et al. Plasma microRNA profiling reveals loss of endothelial miR-126 and other microRNAs in type 2 diabetes. Circ Res. 2010;107(6):810-817.
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23. Liu R, Liu CM, Cui LL, Zhou L, Li N, Wei XD. Expression and significance of MiR-126 and VEGF in proliferative diabetic retinopathy. Eur Rev Med Pharmacol Sci. 2019;23(15):6387-6393.
24. Zhang Q, Kandic I, Kutryk MJ. Dysregulation of angiogenesis-related microRNAs in endothelial progenitor cells from patients with coronary artery disease. Biochem Biophys Res Commun. 2011;405(1):42-46.
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26. Jiang Y, Wang HY, Li Y, Guo SH, Zhang L, Cai JH. Peripheral blood miRNAs as a biomarker for chronic cardiovascular diseases. Sci Rep. 2014;4:5026.
27. Gao J, Yang S, Wang K, Zhong Q, Ma A, Pan X. Plasma miR-126 and miR-143 as Potential Novel Biomarkers for Cerebral Atherosclerosis. J Stroke Cerebrovasc Dis. 2019;28(1):38-43.
28. Chen J, Cui C, Yang X, et al. MiR-126 Affects Brain-Heart Interaction after Cerebral Ischemic Stroke. Transl Stroke Res. 2017;8(4):374-385.
29. Jakob P, Doerries C, Briand S, et al. Loss of angiomiR-126 and 130a in angiogenic early outgrowth cells from patients with chronic heart failure: role for impaired in vivo neovascularization and cardiac repair capacity. Circulation. 2012;126(25):2962-2975.
30. Potus F, Ruffenach G, Dahou A, et al. Downregulation of MicroRNA-126 Contributes to the Failing Right Ventricle in Pulmonary Arterial Hypertension. Circulation. 2015;132(10):932-943.
31. Sun J, Zhang Z, Ma T, et al. Endothelial progenitor cell-derived exosomes, loaded with miR-126, promoted deep vein thrombosis resolution and recanalization. Stem Cell Res Ther. 2018;9(1):223.
32. Fan JL, Zhang L, Bo XH. MiR-126 on mice with coronary artery disease by targeting S1PR2. Eur Rev Med Pharmacol Sci. 2020;24(2):893-904.
33. Schober A, Nazari-Jahantigh M, Wei Y, et al. MicroRNA-126-5p promotes endothelial proliferation and limits atherosclerosis by suppressing Dlk1. Nat Med. 2014;20(4):368-376.
34. Jansen F, Stumpf T, Proebsting S, et al. Intercellular transfer of miR-126-3p by endothelial microparticles reduces vascular smooth muscle cell proliferation and limits neointima formation by inhibiting LRP6. J Mol Cell Cardiol. 2017;104:43-52.
35. Hao XZ, Fan HM. Identification of miRNAs as atherosclerosis biomarkers and functional role of miR-126 in atherosclerosis progression through MAPK signalling pathway. Eur Rev Med Pharmacol Sci. 2017;21(11):2725-2733.
36. Rawal S, Munasinghe PE, Shindikar A, et al. Down-regulation of proangiogenic microRNA-126 and microRNA-132 are early modulators of diabetic cardiac microangiopathy. Cardiovascular Research. 2017;113(1):90-101.
37. McAuley AK, Dirani M, Wang JJ, Connell PP, Lamoureux EL, Hewitt AW. A genetic variant regulating miR-126 is associated with sight threatening diabetic retinopathy. Diabetes Vasc Dis Re. 2015;12(2):133-138.
38. Zhou Q, Anderson C, Hanus J, et al. Strand and Cell Type-specific Function of microRNA-126 in Angiogenesis. Molecular Therapy. 2016;24(10):1823-1835.
39. Wang L, Lee AY, Wigg JP, Peshavariya H, Liu P, Zhang H. miR-126 Regulation of Angiogenesis in Age-Related Macular Degeneration in CNV Mouse Model. Int J Mol Sci. 2016;17(6).
40. Bai X, Luo J, Zhang X, et al. MicroRNA-126 Reduces Blood-Retina Barrier Breakdown via the Regulation of VCAM-1 and BCL2L11 in Ischemic Retinopathy. Ophthalmic Res. 2017;57(3):173-185.
41. Fu X, Niu T, Li X. MicroRNA-126-3p Attenuates Intracerebral Hemorrhage-Induced Blood-Brain Barrier Disruption by Regulating VCAM-1 Expression. Front Neurosci. 2019;13:866.
42. Hu J, Zeng L, Huang J, Wang G, Lu H. miR-126 promotes angiogenesis and attenuates inflammation after contusion spinal cord injury in rats. Brain Res. 2015;1608:191-202.
43. Qu M, Pan J, Wang L, et al. MicroRNA-126 Regulates Angiogenesis and Neurogenesis in a Mouse Model of Focal Cerebral Ischemia. Molecular Therapy - Nucleic Acids. 2019;16:15-25.
44. Chen L, Wang J, Wang B, et al. MiR-126 inhibits vascular endothelial cell apoptosis through targeting PI3K/Akt signaling. Ann Hematol. 2016;95(3):365-374.
45. Pan X, Hou R, Ma A, et al. Atorvastatin Upregulates the Expression of miR-126 in Apolipoprotein E-knockout Mice with Carotid Atherosclerotic Plaque. Cell Mol Neurobiol. 2017;37(1):29-36.
46. Harris TA, Yamakuchi M, Ferlito M, Mendell JT, Lowenstein CJ. MicroRNA-126 regulates endothelial expression of vascular cell adhesion molecule 1. Proc Natl Acad Sci U S A. 2008;105(5):1516-1521.
47. Schmidt M, Paes K, De Maziere A, et al. EGFL7 regulates the collective migration of endothelial cells by restricting their spatial distribution. Development. 2007;134(16):2913-2923.
48. Villain G, Poissonnier L, Noueihed B, et al. miR-126-5p promotes retinal endothelial cell survival through SetD5 regulation in neurons. Development. 2018;145(1).
49. Yan T, Liu Y, Cui K, Hu B, Wang F, Zou L. MicroRNA-126 regulates EPCs function: implications for a role of miR-126 in preeclampsia. J Cell Biochem. 2013;114(9):2148-2159.
50. Chen HX, Li LM, Wang SJ, et al. Reduced miR-126 expression facilitates angiogenesis of gastric cancer through its regulation on VEGF-A. Oncotarget. 2014;5(23):11873-11885.
51. Orso F, Quirico L, Dettori D, et al. Role of miRNAs in tumor and endothelial cell interactions during tumor progression. Semin Cancer Biol. 2020;60:214-224.
52. Guo C, Sah JF, Beard L, Willson JK, Markowitz SD, Guda K. The noncoding RNA, miR-126, suppresses the growth of neoplastic cells by targeting phosphatidylinositol 3-kinase signaling and is frequently lost in colon cancers. Genes Chromosomes Cancer. 2008;47(11):939-946.
53. Lin Q, Hou S, Dai Y, Jiang N, Lin Y. LncRNA HOTAIR targets miR-126-5p to promote the progression of Parkinson's disease through RAB3IP. Biol Chem. 2019;400(9):1217-1228.
54. Jiang B, Tang Y, Wang H, et al. Down-regulation of long non-coding RNA HOTAIR promotes angiogenesis via regulating miR-126/SCEL pathways in burn wound healing. Cell death & disease. 2020;11(1):61-61.
55. Li H, Chen S, Liu J, et al. Long non-coding RNA PVT1-5 promotes cell proliferation by regulating miR-126/SLC7A5 axis in lung cancer. Biochem Biophys Res Commun. 2018;495(3):2350-2355.
56. Geng W, Tang H, Luo S, et al. Exosomes from miRNA-126-modified ADSCs promotes functional recovery after stroke in rats by improving neurogenesis and suppressing microglia activation. Am J Transl Res. 2019;11(2):780-792.
2. Wang SS, Olson EN. AngiomiRs-Key regulators of angiogenesis. Curr Opin Genet Dev. 2009;19(3):205-211.
3. Wang S, Aurora AB, Johnson BA, et al. The endothelial-specific microRNA miR-126 governs vascular integrity and angiogenesis. Dev Cell. 2008;15(2):261-271.
4. Fish JE, Santoro MM, Morton SU, et al. miR-126 regulates angiogenic signaling and vascular integrity. Dev Cell. 2008;15(2):272-284.
5. Kuhnert F, Mancuso MR, Hampton J, et al. Attribution of vascular phenotypes of the murine Egfl7 locus to the microRNA miR-126. Development. 2008;135(24):3989-3993.
6. Zhou Q, Yu B, Anderson C, et al. LncEGFL7OS regulates human angiogenesis by interacting with MAX at the EGFL7/miR-126 locus. Elife. 2019;8.
7. Landgraf P, Rusu M, Sheridan R, et al. A mammalian microRNA expression atlas based on small RNA library sequencing. Cell. 2007;129(7):1401-1414.
8. Kontarakis Z, Rossi A, Ramas S, Dellinger MT, Stainier DYR. Mir-126 is a conserved modulator of lymphatic development. Dev Biol. 2018;437(2):120-130.
9. Mahamud MR, Geng X, Ho YC, et al. GATA2 controls lymphatic endothelial cell junctional integrity and lymphovenous valve morphogenesis through miR-126. Development. 2019;146(21).
10. Chistiakov DA, Orekhov AN, Bobryshev YV. The role of miR-126 in embryonic angiogenesis, adult vascular homeostasis, and vascular repair and its alterations in atherosclerotic disease. J Mol Cell Cardiol. 2016;97:47-55.
11. Sun P, Liu DZ, Jickling GC, Sharp FR, Yin KJ. MicroRNA-based therapeutics in central nervous system injuries. J Cereb Blood Flow Metab. 2018;38(7):1125-1148.
12. Long G, Wang F, Li H, et al. Circulating miR-30a, miR-126 and let-7b as biomarker for ischemic stroke in humans. BMC Neurol. 2013;13:178.
13. Fichtlscherer S, De Rosa S, Fox H, et al. Circulating microRNAs in patients with coronary artery disease. Circ Res. 2010;107(5):677-684.
14. Wang JN, Yan YY, Guo ZY, Jiang YJ, Liu LL, Liu B. Negative Association of Circulating MicroRNA-126 with High-sensitive C-reactive Protein and Vascular Cell Adhesion Molecule-1 in Patients with Coronary Artery Disease Following Percutaneous Coronary Intervention. Chinese Med J-Peking. 2016;129(23):2786-2791.
15. Hsu A, Chen SJ, Chang YS, Chen HC, Chu PH. Systemic approach to identify serum microRNAs as potential biomarkers for acute myocardial infarction. Biomed Res Int. 2014;2014:418628.
16. Fujii R, Yamada H, Yamazaki M, et al. Circulating microRNAs (miR-126, miR-197, and miR-223) are associated with chronic kidney disease among elderly survivors of the Great East Japan Earthquake. BMC Nephrol. 2019;20(1):474.
17. Fourdinier O, Schepers E, Metzinger-Le Meuth V, et al. Serum levels of miR-126 and miR-223 and outcomes in chronic kidney disease patients. Sci Rep. 2019;9(1):4477.
18. Wang H, Peng W, Shen X, Huang Y, Ouyang X, Dai Y. Circulating levels of inflammation-associated miR-155 and endothelial-enriched miR-126 in patients with end-stage renal disease. Braz J Med Biol Res. 2012;45(12):1308-1314.
19. Wei XJ, Han M, Yang FY, et al. Biological significance of miR-126 expression in atrial fibrillation and heart failure. Braz J Med Biol Res. 2015;48(11):983-989.
20. Zampetaki A, Kiechl S, Drozdov I, et al. Plasma microRNA profiling reveals loss of endothelial miR-126 and other microRNAs in type 2 diabetes. Circ Res. 2010;107(6):810-817.
21. Sun X, Zhang M, Sanagawa A, et al. Circulating microRNA-126 in patients with coronary artery disease: correlation with LDL cholesterol. Thromb J. 2012;10(1):16.
22. Jansen F, Yang X, Hoelscher M, et al. Endothelial microparticle-mediated transfer of MicroRNA-126 promotes vascular endothelial cell repair via SPRED1 and is abrogated in glucose-damaged endothelial microparticles. Circulation. 2013;128(18):2026-2038.
23. Liu R, Liu CM, Cui LL, Zhou L, Li N, Wei XD. Expression and significance of MiR-126 and VEGF in proliferative diabetic retinopathy. Eur Rev Med Pharmacol Sci. 2019;23(15):6387-6393.
24. Zhang Q, Kandic I, Kutryk MJ. Dysregulation of angiogenesis-related microRNAs in endothelial progenitor cells from patients with coronary artery disease. Biochem Biophys Res Commun. 2011;405(1):42-46.
25. Meng S, Cao JT, Zhang B, Zhou Q, Shen CX, Wang CQ. Downregulation of microRNA-126 in endothelial progenitor cells from diabetes patients, impairs their functional properties, via target gene Spred-1. J Mol Cell Cardiol. 2012;53(1):64-72.
26. Jiang Y, Wang HY, Li Y, Guo SH, Zhang L, Cai JH. Peripheral blood miRNAs as a biomarker for chronic cardiovascular diseases. Sci Rep. 2014;4:5026.
27. Gao J, Yang S, Wang K, Zhong Q, Ma A, Pan X. Plasma miR-126 and miR-143 as Potential Novel Biomarkers for Cerebral Atherosclerosis. J Stroke Cerebrovasc Dis. 2019;28(1):38-43.
28. Chen J, Cui C, Yang X, et al. MiR-126 Affects Brain-Heart Interaction after Cerebral Ischemic Stroke. Transl Stroke Res. 2017;8(4):374-385.
29. Jakob P, Doerries C, Briand S, et al. Loss of angiomiR-126 and 130a in angiogenic early outgrowth cells from patients with chronic heart failure: role for impaired in vivo neovascularization and cardiac repair capacity. Circulation. 2012;126(25):2962-2975.
30. Potus F, Ruffenach G, Dahou A, et al. Downregulation of MicroRNA-126 Contributes to the Failing Right Ventricle in Pulmonary Arterial Hypertension. Circulation. 2015;132(10):932-943.
31. Sun J, Zhang Z, Ma T, et al. Endothelial progenitor cell-derived exosomes, loaded with miR-126, promoted deep vein thrombosis resolution and recanalization. Stem Cell Res Ther. 2018;9(1):223.
32. Fan JL, Zhang L, Bo XH. MiR-126 on mice with coronary artery disease by targeting S1PR2. Eur Rev Med Pharmacol Sci. 2020;24(2):893-904.
33. Schober A, Nazari-Jahantigh M, Wei Y, et al. MicroRNA-126-5p promotes endothelial proliferation and limits atherosclerosis by suppressing Dlk1. Nat Med. 2014;20(4):368-376.
34. Jansen F, Stumpf T, Proebsting S, et al. Intercellular transfer of miR-126-3p by endothelial microparticles reduces vascular smooth muscle cell proliferation and limits neointima formation by inhibiting LRP6. J Mol Cell Cardiol. 2017;104:43-52.
35. Hao XZ, Fan HM. Identification of miRNAs as atherosclerosis biomarkers and functional role of miR-126 in atherosclerosis progression through MAPK signalling pathway. Eur Rev Med Pharmacol Sci. 2017;21(11):2725-2733.
36. Rawal S, Munasinghe PE, Shindikar A, et al. Down-regulation of proangiogenic microRNA-126 and microRNA-132 are early modulators of diabetic cardiac microangiopathy. Cardiovascular Research. 2017;113(1):90-101.
37. McAuley AK, Dirani M, Wang JJ, Connell PP, Lamoureux EL, Hewitt AW. A genetic variant regulating miR-126 is associated with sight threatening diabetic retinopathy. Diabetes Vasc Dis Re. 2015;12(2):133-138.
38. Zhou Q, Anderson C, Hanus J, et al. Strand and Cell Type-specific Function of microRNA-126 in Angiogenesis. Molecular Therapy. 2016;24(10):1823-1835.
39. Wang L, Lee AY, Wigg JP, Peshavariya H, Liu P, Zhang H. miR-126 Regulation of Angiogenesis in Age-Related Macular Degeneration in CNV Mouse Model. Int J Mol Sci. 2016;17(6).
40. Bai X, Luo J, Zhang X, et al. MicroRNA-126 Reduces Blood-Retina Barrier Breakdown via the Regulation of VCAM-1 and BCL2L11 in Ischemic Retinopathy. Ophthalmic Res. 2017;57(3):173-185.
41. Fu X, Niu T, Li X. MicroRNA-126-3p Attenuates Intracerebral Hemorrhage-Induced Blood-Brain Barrier Disruption by Regulating VCAM-1 Expression. Front Neurosci. 2019;13:866.
42. Hu J, Zeng L, Huang J, Wang G, Lu H. miR-126 promotes angiogenesis and attenuates inflammation after contusion spinal cord injury in rats. Brain Res. 2015;1608:191-202.
43. Qu M, Pan J, Wang L, et al. MicroRNA-126 Regulates Angiogenesis and Neurogenesis in a Mouse Model of Focal Cerebral Ischemia. Molecular Therapy - Nucleic Acids. 2019;16:15-25.
44. Chen L, Wang J, Wang B, et al. MiR-126 inhibits vascular endothelial cell apoptosis through targeting PI3K/Akt signaling. Ann Hematol. 2016;95(3):365-374.
45. Pan X, Hou R, Ma A, et al. Atorvastatin Upregulates the Expression of miR-126 in Apolipoprotein E-knockout Mice with Carotid Atherosclerotic Plaque. Cell Mol Neurobiol. 2017;37(1):29-36.
46. Harris TA, Yamakuchi M, Ferlito M, Mendell JT, Lowenstein CJ. MicroRNA-126 regulates endothelial expression of vascular cell adhesion molecule 1. Proc Natl Acad Sci U S A. 2008;105(5):1516-1521.
47. Schmidt M, Paes K, De Maziere A, et al. EGFL7 regulates the collective migration of endothelial cells by restricting their spatial distribution. Development. 2007;134(16):2913-2923.
48. Villain G, Poissonnier L, Noueihed B, et al. miR-126-5p promotes retinal endothelial cell survival through SetD5 regulation in neurons. Development. 2018;145(1).
49. Yan T, Liu Y, Cui K, Hu B, Wang F, Zou L. MicroRNA-126 regulates EPCs function: implications for a role of miR-126 in preeclampsia. J Cell Biochem. 2013;114(9):2148-2159.
50. Chen HX, Li LM, Wang SJ, et al. Reduced miR-126 expression facilitates angiogenesis of gastric cancer through its regulation on VEGF-A. Oncotarget. 2014;5(23):11873-11885.
51. Orso F, Quirico L, Dettori D, et al. Role of miRNAs in tumor and endothelial cell interactions during tumor progression. Semin Cancer Biol. 2020;60:214-224.
52. Guo C, Sah JF, Beard L, Willson JK, Markowitz SD, Guda K. The noncoding RNA, miR-126, suppresses the growth of neoplastic cells by targeting phosphatidylinositol 3-kinase signaling and is frequently lost in colon cancers. Genes Chromosomes Cancer. 2008;47(11):939-946.
53. Lin Q, Hou S, Dai Y, Jiang N, Lin Y. LncRNA HOTAIR targets miR-126-5p to promote the progression of Parkinson's disease through RAB3IP. Biol Chem. 2019;400(9):1217-1228.
54. Jiang B, Tang Y, Wang H, et al. Down-regulation of long non-coding RNA HOTAIR promotes angiogenesis via regulating miR-126/SCEL pathways in burn wound healing. Cell death & disease. 2020;11(1):61-61.
55. Li H, Chen S, Liu J, et al. Long non-coding RNA PVT1-5 promotes cell proliferation by regulating miR-126/SLC7A5 axis in lung cancer. Biochem Biophys Res Commun. 2018;495(3):2350-2355.
56. Geng W, Tang H, Luo S, et al. Exosomes from miRNA-126-modified ADSCs promotes functional recovery after stroke in rats by improving neurogenesis and suppressing microglia activation. Am J Transl Res. 2019;11(2):780-792.