The progress on the role of miR-126 in the pathogenesis, diagnosis and treatment of diabetic retinopathy_Chinese Journal of Ocular Fundus Diseases

Authors：

Wang Rui ¹ ,  Luo Xiangxia ² , Hu Tingting ¹ , Zhang Yujie ¹

1. Gansu University of Traditional Chinese Medicine, Lanzhou 750000, China;
2. Gansu Hospital of Traditional Chinese Medicine, Lanzhou 730050, China;

Corresponding author：

Luo Xiangxia, Email: jessica_lxx@163.com

Keywords：

Diabetic retinopathy; Microvessels; Review; miR-126

DOI：

10.3760/cma.j.cn511434-20201103-00531

Video：

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Abstract Full text Figures/Tables Video References Cited by

Microvascular dysfunction is a key pathological mechanism of diabetic retinopathy (DR). In recent years, it has been found that the phenomenon of "metabolic memory" is prevalent in diabetic patients, and diabetic microangiopaplasia cannot be avoided even if patients’ blood glucose is well controlled. Therefore, it is necessary to explore DR from a genetic perspective. miR-126 is the unique microRNA specifically expressed in vascular endothelial cells, which is closely related to the formation of neovascularization and can affect the stability of DR microvessels as well as the germination and migration of endothelial cells, and its gene level is significantly negatively correlated with the expression of vascular endothelial cell growth factor. The potential value of intracellular and circulating miR-126 in the regulation of DR microvascular homeostasis, early diagnosis and treatment, and monitoring of disease course has attracted great attention. However, studies in this area are mostly hypothesis-driven and still have some limitations. It is believed that with the rapid development of genomics, the miRNA spectrum and its molecular mechanism in eye development and eye diseases will gradually become clear, which may lead to a breakthrough in the intervention of individual refractory retinal diseases and establish a new miRNA diagnosis and treatment method in the future.

Citation： Wang Rui, Luo Xiangxia, Hu Tingting, Zhang Yujie. The progress on the role of miR-126 in the pathogenesis, diagnosis and treatment of diabetic retinopathy. Chinese Journal of Ocular Fundus Diseases, 2021, 37(11): 906-910. doi: 10.3760/cma.j.cn511434-20201103-00531 Copy

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1. Lagos-Quintana M, Rauhut R, Yalcin A, et al. Identification of tissue-specific microRNAs from mouse[J]. Curr Biol, 2002, 12(9): 735-739. DOI: 10.1016/s0960-9822(02)00809-6.
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3. Nikolic I, Plate KH, Schmidt MHH. EGFL7 meets miRNA-126: an angiogenesis alliance[J/OL]. J Angiogenes Res, 2010, 2(1): 9[2010-06-08]. https://pubmed.ncbi.nlm.nih.gov/20529320/. DOI: 10.1186/2040-2384-2-9.
4. Hu MH, Ma CY, Wang XM, et al. MicroRNA-126 inhibits tumor proliferation and angiogenesis of hepatocellular carcinoma by down-regulating EGFL7 expression[J]. Oncotarget, 2016, 7(41): 66922-66934. DOI: 10.18632/oncotarget.11877.
5. Sohel MMH. Circulating microRNAs as biomarkers in cancer diagnosis[J/OL]. Life Sci, 2020, 248: 117473[2020-05-01]. https://pubmed.ncbi.nlm.nih.gov/32114007/. DOI: 10.1016/j.lfs.2020.117473.
6. Liu CH, Huang S, Britton WR, et al. MicroRNAs in vascular eye diseases[J/OL]. Int J Mol Sci, 2020, 21(2): 649[2020-01-19]. https://pubmed.ncbi.nlm.nih.gov/31963809/. DOI: 10.3390/ijms21020649.
7. Zhou Q, Frost RJA, Anderson C, et al. let-7 contributes to diabetic retinopathy but represses pathological ocular angiogenesis[J/OL]. Mol Cell Biol, 2017, 37(16): e00001-00017[2017-07-28]. https://pubmed.ncbi.nlm.nih.gov/28584193/. DOI: 10.1128/MCB.00001-17.
8. Pastukh N, Meerson A, Kalish D, et al. Serum miR-122 levels correlate with diabetic retinopathy[J]. Clin Exp Med, 2019, 19(2): 255-260. DOI: 10.1007/s10238-019-00546-x.
9. 高宁宁, 宋凡倩, 葛红岩. miR-126与眼科疾病的研究进展[J]. 国际眼科杂志, 2017, 17(6): 1066-1068. DOI: 10.3980/j.issn.1672-5123.2017.6.14.Gao NN, Song FQ, Ge HY. Research advances of miR-126 and ophthalmic diseases[J]. Int Eye Sci, 2017, 17(6): 1066-1068. DOI: 10.3980/j.issn.1672-5123.2017.6.14.
10. Zhang D, Li Z, Wang Z, et al. MicroRNA-126: a promising biomarker for angiogenesis of diabetic wounds treated with negative pressure wound therapy[J]. Diabetes Metab Syndr Obes, 2019, 12: 1685-1696. DOI: 10.2147/DMSO.S199705.
11. Alique M, Bodega G, Giannarelli C, et al. MicroRNA-126 regulates hypoxia-inducible factor-1α which inhibited migration, proliferation, and angiogenesis in replicative endothelial senescence[J/OL]. Sci Rep, 2019, 9(1): 7381[2019-05-14]. https://pubmed.ncbi.nlm.nih.gov/31089163/. DOI: 10.1038/s41598-019-43689-3.
12. Chen Z, Miao F, Paterson AD, et al. Epigenomic profiling reveals an association between persistence of DNA methylation and metabolic memory in the DCCT/EDIC type 1 diabetes cohort[J/OL]. Proc Natl Acad Sci USA, 2016, 113(21): e3002-3011[2016-05-24]. https://pubmed.ncbi.nlm.nih.gov/27162351/. DOI: 10.1073/pnas.1603712113.
13. Kowluru RA, Mohammad G. Epigenetics and mitochondrial stability in the metabolic memory phenomenon associated with continued progression of diabetic retinopathy[J/OL]. Sci Rep, 2020, 10(1): 6655[2020-04-20]. https://pubmed.ncbi.nlm.nih.gov/32313015/. DOI: 10.1038/s41598-020-63527-1.
14. Wang L, Lee AY, Wigg JP, et al. miR-126 regulation of angiogenesis in age-related macular degeneration in CNV mouse model[J/OL]. Int J Mol Sci, 2016, 17(6): 895[2016-06-07]. https://pubmed.ncbi.nlm.nih.gov/27338342/. DOI: 10.3390/ijms17060895.
15. 魏文斌. 糖尿病视网膜病变魏文斌2017观点[M]. 北京: 科学技术文献出版社, 2017: 11-13.Wei WB. Diabetic retinopathy of Wei Wenbin 2017 views[M]. Beijing: Scientific and Technical Literature Publishing House, 2017: 11-13.
16. Li Q, Cheng K, Wang AY, et al. microRNA-126 inhibits tube formation of HUVECs by interacting with EGFL7 and down-regulating PI3K/AKT signaling pathway[J/OL]. Biomed Pharmacother, 2019, 116: 109007[2019-06-03]. https://pubmed.ncbi.nlm.nih.gov/31170663/. DOI: 10.1016/j.biopha.2019.109007.
17. 何亚非, 黄婷, 刘艳霞, 等. 1型糖尿病患者血浆microRNA-126变化与内皮功能的相关性[J]. 中国动脉硬化杂志, 2014, 22(5): 485-488.He YF, Huang T, Liu YX, et al. The relationship between plasma level of microRNA-126 and endothelial function in patients with type 1 diabetes mellitus[J]. Chin J Arterioscler, 2014, 22(5): 485-488.
18. Fish JE, Santoro MM, Morton SU, et al. miR-126 regulates angiogenic signaling and vascular integrity[J/OL]. Dev Cell, 2008, 15(2): 272-284[2008-08-15]. https://pubmed.ncbi.nlm.nih.gov/18694566/. DOI: 10.1016/j.devcel.2008.07.008.
19. 王慧, 温晏, 闫丽, 等. 微小RNA-126在糖尿病视网膜病变患者血浆中的表达及作用机制研究[J]. 中国基层医药, 2016, 23(14): 2134-2137. DOI: 10.3760/cma.j.issn.1008-6706.2016.14.015.Wang H, Wen Y, Yan L, et al. Expressions of microRNA-126 in the blood plasma in patients with diabetic retinopathy and its mechanism[J]. Chin J Prin Med Pharm, 2016, 23(14): 2134-2137. DOI: 10.3760/cma.j.issn.1008-6706.2016.14.015.
20. Chang L, Liang J, Xia X, et al. miRNA-126 enhances viability, colony formation, and migration of keratinocytes HaCaT cells by regulating PI3K/AKT signaling pathway[J]. Cell Biol Int, 2019, 43(2): 182-191. DOI: 10.1002/cbin.11088.
21. Esser JS, Saretzki E, Pankratz F, et al. Bone morphogenetic protein 4 regulates microRNAs miR-494 and miR-126-5p in control of endothelial cell function in angiogenesis[J]. Thromb Haemost, 2017, 117(4): 734-749. DOI: 10.1160/TH16-08-0643.
22. Yang WZ, Yang J, Xue LP, et al. MiR-126 overexpression inhibits high glucose-induced migration and tube formation of rhesus macaque choroid-retinal endothelial cells by obstructing VEGFA and PIK3R2[J]. J Diabetes Complications, 2017, 31(4): 653-663. DOI: 10.1016/j.jdiacomp.2016.12.004.
23. Zou J, Li WQ, Li Q, et al. Two functional microRNA-126s repress a novel target gene p21-activated kinase 1 to regulate vascular integrity in zebrafish[J/OL]. Circ Res, 2011, 108(2): 201-209[2011-01-21]. https://pubmed.ncbi.nlm.nih.gov/21148433/. DOI: 10.1161/CIRCRESAHA.110.225045.
24. van Solingen C, Seghers L, Bijkerk R, et al. Antagomir-mediated silencing of endothelial cell specific microRNA-126 impairs ischemia-induced angiogenesis[J]. J Cell Mol Med, 2009, 13(8A): 1577-1585. DOI: 10.1111/j.1582-4934.2008.00613.x.
25. Nammian P, Razban V, Tabei SMB, et al. MicroRNA-126: dual role in angiogenesis dependent diseases[J]. Curr Pharm Des, 2020, 26(38): 4883-4893. DOI: 10.2174/1381612826666200504120737.
26. Ishizaki T, Tamiya T, Taniguchi K, et al. miR126 positively regulates mast cell proliferation and cytokine production through suppressing spred1[J]. Genes Cells, 2011, 16(7): 803-814. DOI: 10.1111/j.1365-2443.2011.01529.x.
27. Mazzeo A, Beltramo E, Iavello A, et al. Molecular mechanisms of extracellular vesicle-induced vessel destabilization in diabetic retinopathy[J]. Acta Diabetol, 2015, 52(6): 1113-1119. DOI: 10.1007/s00592-015-0798-9.
28. Bai Y, Bai X, Wang Z, et al. MicroRNA-126 inhibits ischemia-induced retinal neovascularization via regulating angiogenic growth factors[J]. Exp Mol Pathol, 2011, 91(1): 471-477. DOI: 10.1016/j.yexmp.2011.04.016.
29. Chen P, Gu YY, Ma FC, et al. Expression levels and co-targets of miRNA-126-3p and miRNA-126-5p in lung adenocarcinoma tissues: an exploration with RT-qPCR, microarray and bioinformatic analyses[J]. Oncol Rep, 2019, 41(2): 939-953. DOI: 10.3892/or.2018.6901.
30. Zhao F, Anderson C, Karnes S, et al. Expression, regulation and function of miR-126 in the mouse choroid vasculature[J]. Exp Eye Res, 2018, 170: 169-176. DOI: 10.1016/j.exer.2018.02.026.
31. 王璐, 张洲铭, 金诺, 等. miR-126多基因靶向调控血管再生的研究[J]. 实用口腔医学杂志, 2019, 35(3): 340-344. DOI: 10.3969/j.issn.1001-3733.2019.03.004.Wang L, Zhang ZM, Jin N, et al. miR-126 promotes vascularization by regulating multiple angiogenesis genes[J]. J Pract Stomatol, 2019, 35(3): 340-344. DOI: 10.3969/j.issn.1001-3733.2019.03.004.
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