长链非编码RNA在糖尿病视网膜病变发展及治疗中的研究进展
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摘要
DR是世界各地工作年龄段成年人失明的主要原因,其发病机制是多因素的,分子机制尚不完全清楚。长链非编码RNA(lncRNAs)被认为是多细胞功能的关键调节因子,已有证据表明其参与了DR的许多病理生理机制,本文就lncRNAs在DR中发挥功能的分子机制及调控作用进行综述,为今后DR的防治研究提供一定的策略和方向。
Diabetic retinopathy(DR) is the main cause of adult blindness in working-age adults around the world.Its pathogenesis is multifactorial and the molecular mechanism is not yet fully understood.Long non-coding RNAs(lncRNAs) are considered to be the major regulators of multicellular function.There is evidence that they are involved in many pathophysiological mechanisms of DR.This article reviews the molecular mechanisms and regulation of lncRNAs functioning in DR to provide a positive strategy and direction for future DR studies.
Diabetic retinopathy(DR) is the main cause of adult blindness in working-age adults around the world.Its pathogenesis is multifactorial and the molecular mechanism is not yet fully understood.Long non-coding RNAs(lncRNAs) are considered to be the major regulators of multicellular function.There is evidence that they are involved in many pathophysiological mechanisms of DR.This article reviews the molecular mechanisms and regulation of lncRNAs functioning in DR to provide a positive strategy and direction for future DR studies.
引文
[1] ZHANG J,CHEN M,CHEN J,LIN S,CAI D,CHEN C,et al.Long non-coding RNA MIAT acts as a biomarker in diabetic retinopathy by absorbing miR-29b and regulating cell apoptosis[J].Bioscience Rep,2017,37(2):BSR20170036.
[2] DAS A.Diabetic retinopathy:battling the global epidemic[J].Invest Ophth Vis Sci,2016,57(15):6669-6682.
[3] YANG Y,TIAN M,LV H B.Recent advances in treatment of diabetic retinopathy[J].Rec Adv Ophthalmol,2015,35(5):497-500.杨宇,田敏,吕红彬.糖尿病视网膜病变的治疗进展[J].眼科新进展,2015,35(5):497-500.
[4] LI C P,WANG S H,WANG W Q,SONG S G,LIU X M.Long noncoding RNA-Sox2OT knockdown alleviates diabetes mellitus-induced retinal ganglion cell (RGC) injury[J].Cell Mol Neurobiol,2017,37(2):361-369.
[5] JAE N,DIMMELER S.Long noncoding RNAs in diabetic retinopathy[J].Circ Res,2015,116(7):1104-1106.
[6] YAN B,YAO J,LIU J Y,LI X M,WANG X Q,LI Y J,et al.LncRNA-MIAT regulates microvascular dysfunction by functioning as a competing endogenous RNA[J].Circ Res,2015,116(7):1143-1156.
[7] CARNINCI P,KASUKAWA T,KATAYAMA S,GOUGH J,FRITH MC,MAEDA N,et al.The transcriptional landscape of the mammalian genome[J].Science,2005,309(5740):1559-1563.
[8] LETI F,DISTEFANO J K.Long noncoding RNAs as diagnostic and therapeutic targets in Type 2 diabetes and related complications[J].Genes,2017,8(8):E207.
[9] CHENG S,WANG L,DENG C H,DU S C,HAN Z G.ARID1A represses hepatocellular carcinoma cell proliferation and migration through lncRNA MVIH[J].Bioch Bioph Res Co,2017,491(1):178-182.
[10] ZHAO F Y,QU Y,LI S P,LIU H T,ZHANG L,MU D Z.Long non-coding RNA expression in neonatal rat brain tissue after hypoxic-ischemic injury[J].Chin J Appl Clin Pediatr,2016(5):376-379.赵凤艳,屈艺,李世平,刘海婷,张莉,母得志.长链非编码RNA在新生大鼠缺氧缺血脑组织中的表达[J].中华实用儿科临床杂志,2016(5):376-379.
[11] XIANG Q,KANG L H,GUAN H J.Research progress on mechanism of lncRNA in ophthalmology disease[J].Rec Adv Ophthalmol,2017,37(6):579-582.向菁,康丽华,管怀进.LncRNA在眼科疾病发生发展中的作用机制研究进展[J].眼科新进展,2017,37(6):579-582.
[12] WANG K C,CHANG H Y.Molecular mechanisms of long noncoding RNAs[J].Mol Cell,2011,43(6):904-914.
[13] BOON R A,JAE N,HOLDT L,DIMMELER S.Long noncoding RNAs:from clinical genetics to therapeutic targets[J]?J Am Coll Cardiol,2016,67(10):1214-1226.
[14] GONG Q,SU G.Roles of miRNAs and long noncoding RNAs in the progression of diabetic retinopathy[J].Bioscience Rep,2017,37(6):BSR20171157.
[15] THOMAS A A,FENG B,CHAKRABARTI S.ANRIL:A regulator of VEGF in diabetic retinopathy[J].Invest Ophthalmol Vis Sci,2017,58(1):470-480.
[16] MOHAN M,KUMAR R G.LncRNA as a Therapeutic target for angiogenesis[J].Curr Top Med Chem,2016,2017,17,1750-1757.
[17] YAN B,TAO Z F,LI X M,ZHANG H,YAO J,JIANG Q.Aberrant expression of long noncoding RNAs in early diabetic retinopathy[J].Invest Ophthalmol Vis Sci,2014,55(2):941-951.
[18] LIU J,PENG W X,MO Y Y,LUO D.MALAT1-mediated tumorigenesis[J].Front Biosci,2017,22:66-80.
[19] DHAMIJA S,DIEDERICHS S.From junk to master regulators of invasion:lncRNA functions in migration,EMT and metastasis[J].Int J Cancer,2016,139(2):269-280.
[20] LIU J Y,YAO J,LI X M,SONG Y C,WANG X Q,LI Y J,et al.Pathogenic role of lncRNA-MALAT1 in endothelial cell dysfunction in diabetes mellitus[J].Cell Death Dis,2014,5:e1506.
[21] MICHALIK K M,YOU X,MANAVSKI Y,DODDABALLAPUR A,ZORNIG M,BRAUN T,et al.Long noncoding RNA MALAT1 regulates endothelial cell function and vessel growth[J].Circ Res,2014,114(9):1389-1397.
[22] PUTHANVEETIL P,CHEN S,FENG B,GAUTAM A,CHAKRABA-RTI S.Long non-coding RNA MALAT1 regulates hyperglycaemia induced inflammatory process in the endothelial cells[J].J Cell Mol Med,2015,19(6):1418-1425.
[23] ZHOU R M,WANG X Q,YAO J,SHEN Y,CHEN S N,YANG H,et al.Identification and characterization of proliferative retinopathy-related long noncoding RNAs[J].Biochem Bioph Res Co,2015,465(3):324-330.
[24] YANG S,YAO H,LI M,LI H,WANG F.Long non-coding RNA MALAT1 mediates transforming growth factor beta1-induced epithelial-mesenchymal transition of retinal pigment epithelial cells[J].PLoS One,2016,11(3):e0152687.
[25] DE ROSA S,ARCIDIACONO B,CHIEFARI E,BRUNETTI A,INDOLFI C,FOTI D P.Type 2 diabetes mellitus and cardiovascular disease:genetic and epigenetic links[J].Front Endocrinol,2018,9:2.
[26] YAP K L,LI S,MUNOZ-CABELLO A M,RAGUZ S,ZENG L,MUJTABA S,et al.Molecular interplay of the noncoding RNA ANRIL and methylated histone H3 lysine 27 by polycomb CBX7 in transcriptional silencing of INK4a[J].Mol Cell,2010,38(5):662-674.
[27] ZHANG B,WANG D,JI T F,SHI L,YU J L.Overexpression of lncRNA ANRIL up-regulates VEGF expression and promotes angiogenesis of diabetes mellitus combined with cerebral infarction by activating NF-kappaB signaling pathway in a rat model[J].Oncotarget,2017,8(10):17347-1759.
[28] CHIDLOW G,WOOD J P,SHARMA S,DIMASI D P,BURDON K P,CASSON R J,et al.Ocular expression and distribution of products of the POAG-associated chromosome 9p21 gene region[J].PLoS One,2013,8(9):e75067.
[29] LIU C,LI C P,WANG J J,SHAN K,LIU X,YAN B.RNCR3 knockdown inhibits diabetes mellitus-induced retinal reactive gliosis[J].Bioch Bioph Res Co,2016,479(2):198-203.
[30] SHAN K,LI C P,LIU C,LIU X,YAN B.RNCR3:A regulator of diabetes mellitus-related retinal microvascular dysfunction[J].Bioch Bioph Res Co,2017,482(4):777-783.
[31] SHANGWENCONG Z T,YUNHUAN G,et al.LncRNA RNCR3 promotes Chop expression by sponging miR-185-5p during MDSC differentiation[J].Oncotarget,2017,8(67):111754-111769.
[32] IP J Y,NAKAGAWA S.Long non-coding RNAs in nuclear bodies[J].Dev Growth Differ,2012,54(1):44-54.
[33] RAPICAVOLI N A,POTH E M,BLACKSHAW S.The long noncoding RNA RNCR2 directs mouse retinal cell specification[J].BMC Dev Biol,2010,10:49.
[34] LI F,WEN X,ZHANG H,FAN X.Novel insights into the role of long noncoding RNA in ocular diseases[J].Int J Mol Sci,2016,17(4):478.
[35] LI Z,LI J,JI D,LENG K,XU Y,HUANG L,et al.Overexpressed long noncoding RNA Sox2ot predicts poor prognosis for cholangiocarcinoma and promotes cell proliferation and invasion[J].Gene,2018,645:131-136.
[36] BRIGGS T A,LOKULO-SODIPE K,CHANDLER K E,MACKAY D J,TEMPLE I K.Temple syndrome as a result of isolated hypomethylation of the 14q32 imprinted DLK1/MEG3 region[J].Am J Med Genet,2016,170(1):170-175.
[37] QIU G Z,TIAN W,FU H T,LI C P,LIU B.Long noncoding RNA-MEG3 is involved in diabetes mellitus-related microvascular dysfunction[J].Bioch Bioph Res Co,2016,471(1):135-141.
[38] LIU S Y,DU X F,MA X,GUO J L,LU J M,MA L S.Low plasma levels of brain derived neurotrophic factor are potential risk factors for diabetic retinopathy in Chinese type 2 diabetic patients[J].Mol Cell Endocrinol,2016,420:152-158.
[39] LI Y,XU F,XIAO H,HAN F.Long noncoding RNA BDNF-AS inversely regulated BDNF and modulated high-glucose induced apoptosis in human retinal pigment epithelial cells[J].J Cell Biochem,2018,119(1):817-823.
[40] KAVIARASAN K,JITHU M,ARIF MULLA M,SHARMA T,SIVASANKAR S,DAS U N,et al.Low blood and vitreal BDNF,LXA4 and altered Th1/Th2 cytokine balance are potential risk factors for diabetic retinopathy[J].Metabolism,2015,64(9):958-966.
[41] AWATA T,YAMASHITA H,KURIHARA S,MORITA-OHKUBO T,MIYASHITA Y,KATAYAMA S,et al.A genome-wide association study for diabetic retinopathy in a Japanese population:potential association with a long intergenic non-coding RNA[J].PLoS One,2014,9(11):e111715.
[42] IYER M K,NIKNAFS Y S,MALIK R,SINGHAL U,SAHU A,HOSONO Y,et al.The landscape of long noncoding RNAs in the human transcriptome[J].Nat Genet,2015,47(3):199-208.
[2] DAS A.Diabetic retinopathy:battling the global epidemic[J].Invest Ophth Vis Sci,2016,57(15):6669-6682.
[3] YANG Y,TIAN M,LV H B.Recent advances in treatment of diabetic retinopathy[J].Rec Adv Ophthalmol,2015,35(5):497-500.杨宇,田敏,吕红彬.糖尿病视网膜病变的治疗进展[J].眼科新进展,2015,35(5):497-500.
[4] LI C P,WANG S H,WANG W Q,SONG S G,LIU X M.Long noncoding RNA-Sox2OT knockdown alleviates diabetes mellitus-induced retinal ganglion cell (RGC) injury[J].Cell Mol Neurobiol,2017,37(2):361-369.
[5] JAE N,DIMMELER S.Long noncoding RNAs in diabetic retinopathy[J].Circ Res,2015,116(7):1104-1106.
[6] YAN B,YAO J,LIU J Y,LI X M,WANG X Q,LI Y J,et al.LncRNA-MIAT regulates microvascular dysfunction by functioning as a competing endogenous RNA[J].Circ Res,2015,116(7):1143-1156.
[7] CARNINCI P,KASUKAWA T,KATAYAMA S,GOUGH J,FRITH MC,MAEDA N,et al.The transcriptional landscape of the mammalian genome[J].Science,2005,309(5740):1559-1563.
[8] LETI F,DISTEFANO J K.Long noncoding RNAs as diagnostic and therapeutic targets in Type 2 diabetes and related complications[J].Genes,2017,8(8):E207.
[9] CHENG S,WANG L,DENG C H,DU S C,HAN Z G.ARID1A represses hepatocellular carcinoma cell proliferation and migration through lncRNA MVIH[J].Bioch Bioph Res Co,2017,491(1):178-182.
[10] ZHAO F Y,QU Y,LI S P,LIU H T,ZHANG L,MU D Z.Long non-coding RNA expression in neonatal rat brain tissue after hypoxic-ischemic injury[J].Chin J Appl Clin Pediatr,2016(5):376-379.赵凤艳,屈艺,李世平,刘海婷,张莉,母得志.长链非编码RNA在新生大鼠缺氧缺血脑组织中的表达[J].中华实用儿科临床杂志,2016(5):376-379.
[11] XIANG Q,KANG L H,GUAN H J.Research progress on mechanism of lncRNA in ophthalmology disease[J].Rec Adv Ophthalmol,2017,37(6):579-582.向菁,康丽华,管怀进.LncRNA在眼科疾病发生发展中的作用机制研究进展[J].眼科新进展,2017,37(6):579-582.
[12] WANG K C,CHANG H Y.Molecular mechanisms of long noncoding RNAs[J].Mol Cell,2011,43(6):904-914.
[13] BOON R A,JAE N,HOLDT L,DIMMELER S.Long noncoding RNAs:from clinical genetics to therapeutic targets[J]?J Am Coll Cardiol,2016,67(10):1214-1226.
[14] GONG Q,SU G.Roles of miRNAs and long noncoding RNAs in the progression of diabetic retinopathy[J].Bioscience Rep,2017,37(6):BSR20171157.
[15] THOMAS A A,FENG B,CHAKRABARTI S.ANRIL:A regulator of VEGF in diabetic retinopathy[J].Invest Ophthalmol Vis Sci,2017,58(1):470-480.
[16] MOHAN M,KUMAR R G.LncRNA as a Therapeutic target for angiogenesis[J].Curr Top Med Chem,2016,2017,17,1750-1757.
[17] YAN B,TAO Z F,LI X M,ZHANG H,YAO J,JIANG Q.Aberrant expression of long noncoding RNAs in early diabetic retinopathy[J].Invest Ophthalmol Vis Sci,2014,55(2):941-951.
[18] LIU J,PENG W X,MO Y Y,LUO D.MALAT1-mediated tumorigenesis[J].Front Biosci,2017,22:66-80.
[19] DHAMIJA S,DIEDERICHS S.From junk to master regulators of invasion:lncRNA functions in migration,EMT and metastasis[J].Int J Cancer,2016,139(2):269-280.
[20] LIU J Y,YAO J,LI X M,SONG Y C,WANG X Q,LI Y J,et al.Pathogenic role of lncRNA-MALAT1 in endothelial cell dysfunction in diabetes mellitus[J].Cell Death Dis,2014,5:e1506.
[21] MICHALIK K M,YOU X,MANAVSKI Y,DODDABALLAPUR A,ZORNIG M,BRAUN T,et al.Long noncoding RNA MALAT1 regulates endothelial cell function and vessel growth[J].Circ Res,2014,114(9):1389-1397.
[22] PUTHANVEETIL P,CHEN S,FENG B,GAUTAM A,CHAKRABA-RTI S.Long non-coding RNA MALAT1 regulates hyperglycaemia induced inflammatory process in the endothelial cells[J].J Cell Mol Med,2015,19(6):1418-1425.
[23] ZHOU R M,WANG X Q,YAO J,SHEN Y,CHEN S N,YANG H,et al.Identification and characterization of proliferative retinopathy-related long noncoding RNAs[J].Biochem Bioph Res Co,2015,465(3):324-330.
[24] YANG S,YAO H,LI M,LI H,WANG F.Long non-coding RNA MALAT1 mediates transforming growth factor beta1-induced epithelial-mesenchymal transition of retinal pigment epithelial cells[J].PLoS One,2016,11(3):e0152687.
[25] DE ROSA S,ARCIDIACONO B,CHIEFARI E,BRUNETTI A,INDOLFI C,FOTI D P.Type 2 diabetes mellitus and cardiovascular disease:genetic and epigenetic links[J].Front Endocrinol,2018,9:2.
[26] YAP K L,LI S,MUNOZ-CABELLO A M,RAGUZ S,ZENG L,MUJTABA S,et al.Molecular interplay of the noncoding RNA ANRIL and methylated histone H3 lysine 27 by polycomb CBX7 in transcriptional silencing of INK4a[J].Mol Cell,2010,38(5):662-674.
[27] ZHANG B,WANG D,JI T F,SHI L,YU J L.Overexpression of lncRNA ANRIL up-regulates VEGF expression and promotes angiogenesis of diabetes mellitus combined with cerebral infarction by activating NF-kappaB signaling pathway in a rat model[J].Oncotarget,2017,8(10):17347-1759.
[28] CHIDLOW G,WOOD J P,SHARMA S,DIMASI D P,BURDON K P,CASSON R J,et al.Ocular expression and distribution of products of the POAG-associated chromosome 9p21 gene region[J].PLoS One,2013,8(9):e75067.
[29] LIU C,LI C P,WANG J J,SHAN K,LIU X,YAN B.RNCR3 knockdown inhibits diabetes mellitus-induced retinal reactive gliosis[J].Bioch Bioph Res Co,2016,479(2):198-203.
[30] SHAN K,LI C P,LIU C,LIU X,YAN B.RNCR3:A regulator of diabetes mellitus-related retinal microvascular dysfunction[J].Bioch Bioph Res Co,2017,482(4):777-783.
[31] SHANGWENCONG Z T,YUNHUAN G,et al.LncRNA RNCR3 promotes Chop expression by sponging miR-185-5p during MDSC differentiation[J].Oncotarget,2017,8(67):111754-111769.
[32] IP J Y,NAKAGAWA S.Long non-coding RNAs in nuclear bodies[J].Dev Growth Differ,2012,54(1):44-54.
[33] RAPICAVOLI N A,POTH E M,BLACKSHAW S.The long noncoding RNA RNCR2 directs mouse retinal cell specification[J].BMC Dev Biol,2010,10:49.
[34] LI F,WEN X,ZHANG H,FAN X.Novel insights into the role of long noncoding RNA in ocular diseases[J].Int J Mol Sci,2016,17(4):478.
[35] LI Z,LI J,JI D,LENG K,XU Y,HUANG L,et al.Overexpressed long noncoding RNA Sox2ot predicts poor prognosis for cholangiocarcinoma and promotes cell proliferation and invasion[J].Gene,2018,645:131-136.
[36] BRIGGS T A,LOKULO-SODIPE K,CHANDLER K E,MACKAY D J,TEMPLE I K.Temple syndrome as a result of isolated hypomethylation of the 14q32 imprinted DLK1/MEG3 region[J].Am J Med Genet,2016,170(1):170-175.
[37] QIU G Z,TIAN W,FU H T,LI C P,LIU B.Long noncoding RNA-MEG3 is involved in diabetes mellitus-related microvascular dysfunction[J].Bioch Bioph Res Co,2016,471(1):135-141.
[38] LIU S Y,DU X F,MA X,GUO J L,LU J M,MA L S.Low plasma levels of brain derived neurotrophic factor are potential risk factors for diabetic retinopathy in Chinese type 2 diabetic patients[J].Mol Cell Endocrinol,2016,420:152-158.
[39] LI Y,XU F,XIAO H,HAN F.Long noncoding RNA BDNF-AS inversely regulated BDNF and modulated high-glucose induced apoptosis in human retinal pigment epithelial cells[J].J Cell Biochem,2018,119(1):817-823.
[40] KAVIARASAN K,JITHU M,ARIF MULLA M,SHARMA T,SIVASANKAR S,DAS U N,et al.Low blood and vitreal BDNF,LXA4 and altered Th1/Th2 cytokine balance are potential risk factors for diabetic retinopathy[J].Metabolism,2015,64(9):958-966.
[41] AWATA T,YAMASHITA H,KURIHARA S,MORITA-OHKUBO T,MIYASHITA Y,KATAYAMA S,et al.A genome-wide association study for diabetic retinopathy in a Japanese population:potential association with a long intergenic non-coding RNA[J].PLoS One,2014,9(11):e111715.
[42] IYER M K,NIKNAFS Y S,MALIK R,SINGHAL U,SAHU A,HOSONO Y,et al.The landscape of long noncoding RNAs in the human transcriptome[J].Nat Genet,2015,47(3):199-208.