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Long Noncoding RNA-Sox2OT Knockdown Alleviates Diabetes Mellitus-Induced Retinal Ganglion Cell (RGC) injury

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Abstract

Retinal ganglion cell (RGC) injury is one of the important pathological features of diabetes-induced retinal neurodegeneration. Increasing attention has been paid to find strategies for protecting against RGC injury. Long noncoding RNAs (lncRNAs) have emerged as the key regulators of many cell functions. Here, we show that Sox2OT expression is significantly down-regulated in the retinas of STZ-induced diabetic mice and in the RGCs upon high glucose or oxidative stress. SOX2OT knockdown protects RGCs against high glucose-induced injury in vitro. Moreover, Sox2OT knockdown plays a neuroprotective role in diabetes-related retinal neurodegeneration in vivo. Sox2OT knockdown could regulate oxidative stress response in RGCs and diabetic mouse retinas. Sox2OT knockdown plays an anti-oxidative role via regulating NRF2/HO-1 signaling activity. Taken together, Sox2OT knockdown may be a therapeutic strategy for the prevention and treatment of diabetes-induced retinal neurodegeneration.

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References

  • Alvarez ML, DiStefano JK (2013) The role of non-coding RNAs in diabetic nephropathy: potential applications as biomarkers for disease development and progression. Diabetes Res Clin Pr 99(1):1–11

    Article  CAS  Google Scholar 

  • Amaral PP, Neyt C, Wilkins SJ, Askarian-Amiri ME, Sunkin SM, Perkins AC, Mattick JS (2009) Complex architecture and regulated expression of the Sox2ot locus during vertebrate development. RNA 15(11):2013–2027

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Andrew T, Maniatis N, Carbonaro F, Liew S, Lau W, Spector TD, Hammond CJ (2008) Identification and replication of three novel myopia common susceptibility gene loci on chromosome 3q26 using linkage and linkage disequilibrium mapping. PLoS Genet 4(10):e1000220

    Article  PubMed  PubMed Central  Google Scholar 

  • Askarian-Amiri ME, Seyfoddin V, Smart CE, Wang J, Kim JE, Hansji H, Baguley BC, Finlay GJ, Leung EY (2014) Emerging role of long non-coding RNA SOX2OT in SOX2 regulation in breast cancer

  • Barber AJ, Lieth E, Khin SA, Antonetti DA, Buchanan AG, Gardner TW (1998) Neural apoptosis in the retina during experimental and human diabetes. Early onset and effect of insulin. J Clin Invest 102(4):783–791

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Barber AJ, Gardner TW, Abcouwer SF (2011) The significance of vascular and neural apoptosis to the pathology of diabetic retinopathy. Invest Ophth Vis Sci 52(2):1156–1163

    Article  CAS  Google Scholar 

  • Chen X-L, Dodd G, Thomas S, Zhang X, Wasserman MA, Rovin BH, Kunsch C (2006) Activation of Nrf2/ARE pathway protects endothelial cells from oxidant injury and inhibits inflammatory gene expression. Am J Physiol-heart C 290(5):H1862–H1870

    Article  CAS  Google Scholar 

  • Chen H, Yu M, Li M, Zhao R, Zhu Q, Zhou W, Lu M, Lu Y, Zheng T, Jiang J (2012) Polymorphic variations in manganese superoxide dismutase (MnSOD), glutathione peroxidase-1 (GPX1), and catalase (CAT) contribute to elevated plasma triglyceride levels in Chinese patients with type 2 diabetes or diabetic cardiovascular disease. Mol Cell Biochem 363(1–2):85–91

    Article  CAS  PubMed  Google Scholar 

  • Chen S, Fan Q, Li A, Liao D, Ge J, Laties AM, Zhang X (2013) Dynamic mobilization of PGC-1α mediates mitochondrial biogenesis for the protection of RGC-5 cells by resveratrol during serum deprivation. Apoptosis 18(7):786–799

    Article  CAS  PubMed  Google Scholar 

  • Esteller M (2011) Non-coding RNAs in human disease. Nat Rev Genet 12(12):861–874

    Article  CAS  PubMed  Google Scholar 

  • Fantes J, Ragge NK, Lynch S-A, McGill NI, Collin J, Howard-Peebles PN, Hayward C, Vivian AJ, Williamson K, van Heyningen V (2003) Mutations in SOX2 cause anophthalmia. Nat Genet 33(4):461–463

    Article  CAS  PubMed  Google Scholar 

  • Giacco F, Brownlee M (2010) Oxidative stress and diabetic complications. Circ Res 107(9):1058–1070

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hong S, Iizuka Y, Kim CY, Seong GJ (2012) Isolation of primary mouse retinal ganglion cells using immunopanning-magnetic separation. Mol Vis 18:2922–2930

    CAS  PubMed  PubMed Central  Google Scholar 

  • Hou Z, Zhao W, Zhou J, Shen L, Zhan P, Xu C, Chang C, Bi H, Zou J, Yao X (2014) A long noncoding RNA Sox2ot regulates lung cancer cell proliferation and is a prognostic indicator of poor survival. Intl J Biochem Cell Biol 53:380–388

    Article  CAS  Google Scholar 

  • Jazi MS, Samaei NM, Ghanei M, Shadmehr MB, Mowla SJ (2015) Identification of new SOX2OT transcript variants highly expressed in human cancer cell lines and down regulated in stem cell differentiation. Mol Biol Rep 1–8

  • Jonsson G, Eysteinsson T (2014) The effects of stimulating and blocking the retinal A2A and A3 adenosine receptors on the components of the rat ERG. Invest Ophth Vis Sci 55(13):1888

    Google Scholar 

  • Kern TS, Barber AJ (2008) Retinal ganglion cells in diabetes. The Journal of physiology 586(18):4401–4408

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Liu J, Yao J, Li X, Song Y, Wang X, Li Y, Yan B, Jiang Q (2014) Pathogenic role of lncRNA-MALAT1 in endothelial cell dysfunction in diabetes mellitus. Cell Death Dis 5(10):e1506

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • London A, Benhar I, Schwartz M (2013) The retina as a window to the brain—from eye research to CNS disorders. Nat Rev Neurol 9(1):44–53

    Article  CAS  PubMed  Google Scholar 

  • Mercer TR, Dinger ME, Sunkin SM, Mehler MF, Mattick JS (2008a) Specific expression of long noncoding RNAs in the mouse brain. Proc Natl Acad Sci USA 105(2):716–721

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Mercer TR, Dinger ME, Sunkin SM, Mehler MF, Mattick JS (2008b) Specific expression of long noncoding RNAs in the mouse brain. Proc Natl Acad Sci USA 105(2):716–721

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Mercer TR, Dinger ME, Mattick JS (2009) Long non-coding RNAs: insights into functions. Nat Rev Genet 10(3):155–159

    Article  CAS  PubMed  Google Scholar 

  • Moran VA, Perera RJ, Khalil AM (2012) Emerging functional and mechanistic paradigms of mammalian long non-coding RNAs. Nucleic Acids Res 40(14):6391–6400

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Na H-K, Surh Y-J (2014) Oncogenic potential of Nrf2 and its principal target protein heme oxygenase-1. Free Radical Bio Med 67:353–365

    Article  CAS  Google Scholar 

  • Park H-YL, Kim JH, Park CK (2014) Neuronal cell death in the inner retina and the influence of vascular endothelial growth factor inhibition in a diabetic rat model. Am J Pathol 184(6):1752–1762

    Article  CAS  PubMed  Google Scholar 

  • Shahryari A, Saghaeian-jazi M, Mansour-samaei N, Mowla S (2015) Long non-coding RNA SOX2OT: expression signature, splicing patterns and emerging roles in pluripotency and tumorigenesis. Front Genet 6:196

    Article  PubMed  PubMed Central  Google Scholar 

  • Shi X-M, Teng F (2015) Up-regulation of long non-coding RNA Sox2ot promotes hepatocellular carcinoma cell metastasis and correlates with poor prognosis. Int J Clin Exp Patho 8(4):4008

    CAS  Google Scholar 

  • Wallace C, Smyth DJ, Maisuria-Armer M, Walker NM, Todd JA, Clayton DG (2010) The imprinted DLK1-MEG3 gene region on chromosome 14q32. 2 alters susceptibility to type 1 diabetes. Nat Genet 42(1):68–71

    Article  CAS  PubMed  Google Scholar 

  • Yan B, Yao J, Liu J-Y, Li X-M, Wang X-Q, Li Y-J, Tao Z-F, Song Y-C, Chen Q, Jiang Q (2015) lncRNA-MIAT regulates microvascular dysfunction by functioning as a competing endogenous RNA. Circ Res 116(7):1143–1156

    Article  CAS  PubMed  Google Scholar 

  • Zakkar M, Van der Heiden K, Luong LA, Chaudhury H, Cuhlmann S, Hamdulay SS, Krams R, Edirisinghe I, Rahman I, Carlsen H (2009) Activation of Nrf2 in endothelial cells protects arteries from exhibiting a proinflammatory state. Arterioscl Throm Vas 29(11):1851–1857

    Article  CAS  Google Scholar 

  • Zaverucha-do-Valle C, Mesentier-Louro L, Gubert F, Mortari N, Padilha AB, Paredes BD, Mencalha A, Abdelhay E, Teixeira C, Ferreira FG (2014) Sustained effect of bone marrow mononuclear cell therapy in axonal regeneration in a model of optic nerve crush. Brain Res 1587:54–68

    Article  CAS  PubMed  Google Scholar 

  • Zeng X-Q, Li N, Pan D-Y, Miao Q, Ma G-F, Liu Y-M, Tseng Y-J, Li F, Xu L-L, Chen S-Y (2015) Kruppel-like factor 2 inhibit the angiogenesis of cultured human liver sinusoidal endothelial cells through the ERK1/2 signaling pathway. Biochem Bioph Res Co 464(4):1241–1247

    Article  CAS  Google Scholar 

  • Zhang Y, Shi Y, Qiao L, Sun Y, Ding W, Zhang H, Li N, Chen D (2012) Sigma-1 receptor agonists provide neuroprotection against gp120 via a change in bcl-2 expression in mouse neuronal cultures. Brain Res 1431:13–22

    Article  CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Huai’ an First People’s Hospital, Nanjing Medical University, Huai an, Jiangsu, China

    Chao-Peng Li, Shu-Hong Wang, Wen-Qi Wang, Shu-Guang Song & Xiu-Ming Liu

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  1. Chao-Peng Li
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  2. Shu-Hong Wang
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  3. Wen-Qi Wang
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  4. Shu-Guang Song
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  5. Xiu-Ming Liu
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Correspondence to Chao-Peng Li.

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Li, CP., Wang, SH., Wang, WQ. et al. Long Noncoding RNA-Sox2OT Knockdown Alleviates Diabetes Mellitus-Induced Retinal Ganglion Cell (RGC) injury. Cell Mol Neurobiol 37, 361–369 (2017). https://doi.org/10.1007/s10571-016-0380-1

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