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DOI: 10.1055/a-1982-3926
MiR-99a-5p Inhibits the Proliferation and Migration of Human Retinal Microvascular Endothelial Cells by Targeting NOX4
Funding Information Project supported by Hainan Province Key Laboratory of Ophthalmology- Clinical Medical Center.
Abstract
Diabetic retinopathy is one of the common microvascular complications of diabetes, and it is the main cause of vision loss among working-age people. This study interpreted the roles of miR-99a-5p in DR patients and human retinal microvascular endothelial cell (hRMECs) injury induced by high glucose. The expression of miR-99a-5p was detected in patients with NDR, NPDR, and PDR. The indictive impacts of miR-99a-5p were tested by the ROC curve, and the link between miR-99a-5p and clinical information was verified by the Pearson test. HG was used to instruct cell models. The CCK-8 and transwell methods were performed to detect the proliferative and migrated cells. The targeted relationship was explained by luciferase activity. The content of miR-99a-5p was gradually lessened in NPDR and PDR patients. MiR-99a-5p might differentiate DR patients from NDR patients and PDR patients from NPDR patients. The interconnection between miR-99a-5p and clinical factors was endorsed in all DR patients. Overexpression of miR-99a-5p assuaged the abnormality of cell migration and proliferation of hRMECs triggered by HG. NOX4 was a downstream signaling component of miR-99a-5p. In conclusion, MiR-99a-5p protected hRMECs against HG damage, and the miR-99a-5p might be a novel target for diagnosis of DR.
+ The first two authors contributed equally to this work.
Publikationsverlauf
Eingereicht: 10. August 2022
Angenommen nach Revision: 09. November 2022
Artikel online veröffentlicht:
11. Januar 2023
© 2023. Thieme. All rights reserved.
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References
- 1 Zhao H, Liu H, Yang Y. et al. The role of H(2)S regulating NLRP3 inflammasome in diabetes. Int J Mol Sci 2022; 23: 4818
- 2 Liu H, Yue K, Cheng S. et al. Hybrid model structure for diabetic retinopathy classification. J Healthc Eng 2020;
- 3 He Y, Al-Mureish A, Wu N. Nanotechnology in the treatment of diabetic complications: a comprehensive narrative review. J Diabetes Res 2021;
- 4 Zhang X, Zhang Y, Zhou M. et al. DPHC from alpinia officinarum ameliorates oxidative stress and insulin resistance via activation of Nrf2/ARE pathway in db/db mice and high glucose-treated HepG2 cells. Front Pharmacol 2021; 12: 792977
- 5 Wang Y, Wang L, Zhou H. et al. Application research of artificial intelligence screening system for diabetic retinopathy. J Healthc Eng 2022; 2022: 2185547
- 6 Lin GM, Chen MJ, Yeh CH. et al. Transforming retinal photographs to entropy images in deep learning to improve automated detection for diabetic retinopathy. J Ophthalmol 2018; 2018: 2159702
- 7 Rajalakshmi R, Prathiba V, Rani PK. et al. Various models for diabetic retinopathy screening that can be applied to India. Indian J Ophthalmol 2021; 69: 2951-2958
- 8 Wang J, Han B. Dysregulated CD4+T cells and microRNAs in myocarditis. Front Immunol 2020; 11: 539
- 9 Xu J, Chen Z, Wang Y. et al. Several circulating miRNAs related to hyperlipidemia and atherosclerotic cardiovascular diseases. Lipids Health Dis 2019; 18: 104
- 10 Yu S, Zhao H, Yang W. et al. The alcohol extract of Coreopsis tinctoria nutt ameliorates diabetes and diabetic nephropathy in db/db mice through miR-192/miR-200b and PTEN/AKT and ZEB2/ECM pathways. Biomed Res Int 2019;
- 11 Liang YZ, Dong J, Zhang J. et al. Identification of neuroendocrine stress response-related circulating microRNAs as biomarkers for type 2 diabetes mellitus and insulin resistance. Front Endocrinol (Lausanne) 2018; 9: 132
- 12 Yin Z, Zhao Y, He M. et al. MiR-30c/PGC-1β protects against diabetic cardiomyopathy via PPARα. Cardiovasc Diabetol 2019; 18: 7
- 13 Yang Y, Liu Y, Li Y. et al. MicroRNA-15b targets vegf and inhibits angiogenesis in proliferative diabetic retinopathy. J Clin Endocrinol Metab 2020; 105: 3404-3415
- 14 Ji H, Yi Q, Chen L. et al. Circulating miR-3197 and miR-2116-5p as novel biomarkers for diabetic retinopathy. Clin Chim Acta 2020; 501: 147-153
- 15 Samandari N, Mirza AH, Kaur S. et al. Influence of disease duration on circulating levels of miRNAs in children and adolescents with new onset type 1 diabetes. Noncoding RNA 2018; 4: 35
- 16 Zhu P, Liu J, Lu M. et al. Influence and mechanism of miR-99a suppressing development of colorectal cancer (CRC) with diabetes mellitus (DM). Onco Targets Ther 2019; 12: 10311-10321
- 17 Colman PG, Thomas DW, Zimmet PZ. et al. New classification and criteria for diagnosis of diabetes mellitus. The australasian working party on diagnostic criteria for diabetes mellitus. N Z Med J 1999; 112: 139-141
- 18 Wilkinson CP, Ferris FL, Klein RE. et al. Proposed international clinical diabetic retinopathy and diabetic macular edema disease severity scales. Ophthalmology 2003; 110: 1677-1682
- 19 Liu F, Weng H, Xu R. et al. Nursing interns’ attitudes toward, preferences for, and use of diabetes virtual simulation teaching applications in China: National Web-Based Survey. JMIR mHealth uHealth 2021; 9: e29498
- 20 Yang Z, Lou X, Zhang J. et al. Association between early markers of renal injury and type 2 diabetic peripheral neuropathy. Diabetes Metab Syndr Obes 2021; 14: 4391-4397
- 21 Lee SH, Yang JY, Madrakhimov S. et al. Adeno-associated viral vector 2 and 9 transduction is enhanced in streptozotocin-induced diabetic mouse retina. Mol Ther Methods Clin Dev 2019; 13: 55-66
- 22 Meng C, Gu C, He S. et al. Pyroptosis in the retinal neurovascular unit: new insights into diabetic retinopathy. Front Immunol 2021; 12: 763092
- 23 Abouhish H, Thounaojam MC, Jadeja RN. et al. Inhibition of HDAC6 attenuates diabetes-induced retinal redox imbalance and microangiopathy. Antioxidants (Basel) 2020; 9: 599
- 24 Yu Y, Ren KM, Chen XL. Expression and role of P-element-induced wimpy testis-interacting RNA in diabetic-retinopathy in mice. World J Diabetes 2021; 12: 1116-1130
- 25 Zhu Y, Tian F, Li H. et al. Profiling maternal plasma microRNA expression in early pregnancy to predict gestational diabetes mellitus. Int J Gynaecol Obstet 2015; 130: 49-53
- 26 Garrido-Cano I, Constâncio V, Adam-Artigues A. et al. Circulating miR-99a-5p expression in plasma: a potential biomarker for early diagnosis of breast cancer. Int J Mol Sci 2020; 21: 7427
- 27 Hebbar A, Chandel R, Rani P. et al. Urinary cell-free miR-99a-5p as a potential biomarker for estrus detection in buffalo. Front Vet Sci 2021; 8: 643910
- 28 Lu Z, He Q, Liang J. et al. MiR-31-5p is a potential circulating biomarker and therapeutic target for oral cancer. Mol Ther Nucleic Acids 2019; 16: 471-480
- 29 Zhang Y, Lv X, Hu Z. et al. Protection of Mcc950 against high-glucose-induced human retinal endothelial cell dysfunction. Cell Death Dis 2017; 8: e2941
- 30 Saito R, Maruyama S, Kawaguchi Y. et al. MiR-99a-5p as possible diagnostic and prognostic marker in patients with gastric cancer. J Surg Res 2020; 250: 193-199
- 31 Liu Y, Li B, Yang X. et al. MiR-99a-5p inhibits bladder cancer cell proliferation by directly targeting mammalian target of rapamycin and predicts patient survival. J Cell Biochem 2019; 120: 19330-19337
- 32 Shi Y, Bo Z, Pang G. et al. MiR-99a-5p regulates proliferation, migration and invasion abilities of human oral carcinoma cells by targeting NOX4. Neoplasma 2017; 64: 666-673
- 33 Meng W, Shah KP, Pollack S. et al. A genome-wide association study suggests new evidence for an association of the NADPH Oxidase 4 (NOX4) gene with severe diabetic retinopathy in type 2 diabetes. Acta Ophthalmol 2018; 96: e811-e819
- 34 Yang Y, Zhou M, Liu H. Luteolin, an aryl hydrocarbon receptor antagonist, alleviates diabetic retinopathy by regulating the NLRP/NOX4 signalling pathway: Experimental and molecular docking study. Physiol Int 2021; 108: 172-184
- 35 Gu C, Draga D, Zhou C. et al. MiR-590-3p Inhibits pyroptosis in diabetic retinopathy by targeting NLRP1 and inactivating the NOX4 signaling pathway. Invest Ophthalmol Vis Sci 2019; 60: 4215-4223