风湿性心脏病合并房颤患者Lnc RNA差异性表达研究
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摘要
目的:探讨风湿性心脏病合并心房颤动患者右心耳组织中LncRNA表达变化,为进一步研究心房颤动发生机理提供实验依据。方法:选择风湿性心脏病合并心房颤动患者5例和风湿性心脏病未合并有心房颤动患者5例,外科手术中切下的右心耳组织作为实验样本,分别作为实验组及对照组,采用高通量基因芯片技术检测,获得LncRNA和mRNA差异表达数据,对差异表达的m RNAs进行GO、KEGG等初步生物信息学分析。结果:与对照组LncRNA基因表达谱相比,实验组LncRNA表达水平显著上调有119个(其中有9个Fold change>4倍),表达水平下调有214个(其中有14个Fold change>4倍);Go分析结果中,生物学过程差异基因富集条目169条,细胞组分差异基因富集条目18条,分子生物学差异基因富集条目89条;KEGG分析显示,受差异基因调控通路共18条。结论:LncRNA在房颤患者右心耳组织中存在差异表达,提示LncRNA可能参与房颤发生与发展的调控,并将为进一步研究提供实验依据。
Objective:To investigate the change in the expression of long non-coding RNA(lncRNA) in the auricula dextra in patients with rheumatic heart disease and atrial fibrillation(AF), and to provide an experimental basis for further research on the pathogenesis of AF.Methods:A total of 5 patients with rheumatic heart disease and AF and 5 with rheumatic heart disease alone were enrolled. The auricula dextra tissue samples were collected during surgery and were divided into experimental group and control group. High-throughput gene microarray was used to obtain the data on the differential expression of lncRNA and mRNA, and gene ontology(GO) and Kyoto Encyclopedia of Genes and Genome(KEGG) were used to perform a bioinformatics analysis of differentially expressed mRNAs.Results:Compared with the control group, the experimental group had 119 significantly upregulated lncRNAs(among which 9 had a fold change of > 4 times) and 214 significantly downregulated lncRNAs(among which 14 had a fold change of > 4 times). GO analysis showed 169 significantly enriched biological process terms, 18 significantly enriched cellular component terms, and 89 significantly enriched molecular biology terms. KEGG analyses showed that 18 signaling pathways were regulated by differentially expressed genes.Conclusion:There is differential expression of lncRNAs in the auricula dextra tissue in patients with AF, suggesting that lncRNA might be involved in the regulation of the development and progression of AF, which will provide an experimental basis for further studies.
Objective:To investigate the change in the expression of long non-coding RNA(lncRNA) in the auricula dextra in patients with rheumatic heart disease and atrial fibrillation(AF), and to provide an experimental basis for further research on the pathogenesis of AF.Methods:A total of 5 patients with rheumatic heart disease and AF and 5 with rheumatic heart disease alone were enrolled. The auricula dextra tissue samples were collected during surgery and were divided into experimental group and control group. High-throughput gene microarray was used to obtain the data on the differential expression of lncRNA and mRNA, and gene ontology(GO) and Kyoto Encyclopedia of Genes and Genome(KEGG) were used to perform a bioinformatics analysis of differentially expressed mRNAs.Results:Compared with the control group, the experimental group had 119 significantly upregulated lncRNAs(among which 9 had a fold change of > 4 times) and 214 significantly downregulated lncRNAs(among which 14 had a fold change of > 4 times). GO analysis showed 169 significantly enriched biological process terms, 18 significantly enriched cellular component terms, and 89 significantly enriched molecular biology terms. KEGG analyses showed that 18 signaling pathways were regulated by differentially expressed genes.Conclusion:There is differential expression of lncRNAs in the auricula dextra tissue in patients with AF, suggesting that lncRNA might be involved in the regulation of the development and progression of AF, which will provide an experimental basis for further studies.
引文
1.Wakili R,Voigt N,Kaab S,et al.Recent advances in the molecular pathophysiology of atrail fibrillation[J].Clin Invest,2011,121:2 955-2 968.
2.Ananlia Medeiros,Gomes da Silva,Vivian Nogueira Silbiger.miRNAs as biomarkers of atrial fibrillation[J].Biomarkers,2014,17(2):1 354-1 361.
3.Wapinski O,Chang H1.Long non-coding RNAs and human disease[J].Trends cell boi,201l,21(6):354-361.
4.Xiao B,Zhang XJ,Li Y,et al.Identification,bioinfomatic analysis and expression profiling of candidate Mrnalike non-coding RNAs in Sus scrofa[J].Genet Genonics,2009,36(12):695-702.
5.Wutz A,Rasmussen TP,Jaeniscb R.Chromosomal silencing and localization are mediated by difrent domains of Xist RNA[J].Nat Genet,2002,30(2):l 67-174.
6.Gong C,Maquat LE.1ncRNAs transactivate STAU 1-mediated mRNA decay by duplexing with 3’-UTRs Via Aluelements[J].Nature,201l,470(7333):284-288.
7.Pradeep Poudel,Yanmin Xu,Zhanqian Cui,et al.Atrial fibrillation:recent advances in understanding the role of microRNAs in atrial remodeling with an electrophysiological overview[J].Cardiology,2015,131:58-67.
8.Rinn JL,Kertesz M,Wang JK,et al.Functional demarcation of active and silent chromatin domains in human HOX loci by non-coding RNAs[J].Cell,2007,129(7):1 311-1 123.
9.Klattenhoff CA,Scheuermann JC,Surface LE,et al.Braveheart,a long noncoding RNA required for cardiovas cular lineage commitment[J].Cell,2013,152:570-583.
10.Congrains A,Kamide K,Oguro R,et al.Genetic variants at the 9p21 locus contribute to ath erosclerosis through modulation of ANRIL and CDKN2A/B[J].Atherosclerosis,2012,220:449-455.
11.Ishii N,Ozaki K,Sato H,et al.Identification of a novel non-coding RNA,MIAT,that confers risk of myocardial infarction[J].Hum Genet,2006,51:1 087-1 099.
12.Xu Y,Huang R,Gu J,Jiang W.Identification of long non-coding RNAs as novel biomarker and potential herapeutic arget for atrial fibrillation in old adults[J].Oncotarget,2016,7(10):10 803-10 811
13.?rom UA,Derrien T,Beringer M,et al.Long noncoding RNAs with enhancer-like function in human cells[J].Cell,2010,143(1):46-58.
14.Guttman M,Amit I,Garber M,et al.Chromatin signature reveals over a thousand highly conserved large noncoding RNAs in mammals[J].Nature,2009,458(7235):223-227.
15.Khalil AM,Guttman M,Huarte M,et al.Many human large intergenic noncoding RNAs associate with chromatin-modifying complexes and affect gene expression[J].Proc Natl Acad Sci U S A,2009,106(28):11 667-11 672.
16.Numata,K.Kiyosawa,H.Genome-wide impact of endogenous antisense transcripts in Eukaryotes[J].Front Biosci,2012,17,300-315.
17.Johnsson P,Ackley A,Vidarsdottir L.et al.A pseudogene long-noncoding-RNA network regulates PTEN transcription and translation in human cells[J].Nat.Struct.Mol.Biol,2013,20(4),440-446.
18.Guttman,M.Rinn,J.L.Modular regulatory principles of large non-coding RNAs[J].Nature,2012,482(7 385),339-346.
19.Faust,T.;Frankel,A D’Orso,I.Transcription control by longnon-codingRNAs[J].Transcription,2012;3(2):78-86.
20.Chen,L.L.Carmichael,G.G.Decoding the function of nuclear long non-coding RNAs[J].Curr Opin Cell Biol,2010,22(3):357-364.
21.Bauer EM,Zheng H,Comhair S.et al.Complement C3deficiency attenuates chronic hypoxia-induced pulmonary hypertension in mice[J].PLoS One,2011,6(12):e28 578.
22.Delbeck M,Nickel KF,Perzborn E.et al.A role for coagulation factor Xa in experimental pulmonary arterial hypertension[J].Cardiovasc Res,2011,92(1):159-168.
23.Burstein B,Comtois P,Michael G,et al.Changes in connexin expression and the atrial fibrillation substrate in congestive heart failure[J].Circ Res,2012;105:1 213-1 222.
24.Scott Valastyan,Robert A Weinberg.Roles for microRNAs in the regulation of cell adhesion molecules[J].Cell Sci,2011,124(7):999-1 006.
25.Sudo R,Sato F,Azechi T,et al.MiR-29-mediated elastin down-regulation contributes to inorganic phosphorus-induced osteoblastic differentiation in vascular smooth muscle cells[J].Genes cells,2015,20(12)1 077-1087.
2.Ananlia Medeiros,Gomes da Silva,Vivian Nogueira Silbiger.miRNAs as biomarkers of atrial fibrillation[J].Biomarkers,2014,17(2):1 354-1 361.
3.Wapinski O,Chang H1.Long non-coding RNAs and human disease[J].Trends cell boi,201l,21(6):354-361.
4.Xiao B,Zhang XJ,Li Y,et al.Identification,bioinfomatic analysis and expression profiling of candidate Mrnalike non-coding RNAs in Sus scrofa[J].Genet Genonics,2009,36(12):695-702.
5.Wutz A,Rasmussen TP,Jaeniscb R.Chromosomal silencing and localization are mediated by difrent domains of Xist RNA[J].Nat Genet,2002,30(2):l 67-174.
6.Gong C,Maquat LE.1ncRNAs transactivate STAU 1-mediated mRNA decay by duplexing with 3’-UTRs Via Aluelements[J].Nature,201l,470(7333):284-288.
7.Pradeep Poudel,Yanmin Xu,Zhanqian Cui,et al.Atrial fibrillation:recent advances in understanding the role of microRNAs in atrial remodeling with an electrophysiological overview[J].Cardiology,2015,131:58-67.
8.Rinn JL,Kertesz M,Wang JK,et al.Functional demarcation of active and silent chromatin domains in human HOX loci by non-coding RNAs[J].Cell,2007,129(7):1 311-1 123.
9.Klattenhoff CA,Scheuermann JC,Surface LE,et al.Braveheart,a long noncoding RNA required for cardiovas cular lineage commitment[J].Cell,2013,152:570-583.
10.Congrains A,Kamide K,Oguro R,et al.Genetic variants at the 9p21 locus contribute to ath erosclerosis through modulation of ANRIL and CDKN2A/B[J].Atherosclerosis,2012,220:449-455.
11.Ishii N,Ozaki K,Sato H,et al.Identification of a novel non-coding RNA,MIAT,that confers risk of myocardial infarction[J].Hum Genet,2006,51:1 087-1 099.
12.Xu Y,Huang R,Gu J,Jiang W.Identification of long non-coding RNAs as novel biomarker and potential herapeutic arget for atrial fibrillation in old adults[J].Oncotarget,2016,7(10):10 803-10 811
13.?rom UA,Derrien T,Beringer M,et al.Long noncoding RNAs with enhancer-like function in human cells[J].Cell,2010,143(1):46-58.
14.Guttman M,Amit I,Garber M,et al.Chromatin signature reveals over a thousand highly conserved large noncoding RNAs in mammals[J].Nature,2009,458(7235):223-227.
15.Khalil AM,Guttman M,Huarte M,et al.Many human large intergenic noncoding RNAs associate with chromatin-modifying complexes and affect gene expression[J].Proc Natl Acad Sci U S A,2009,106(28):11 667-11 672.
16.Numata,K.Kiyosawa,H.Genome-wide impact of endogenous antisense transcripts in Eukaryotes[J].Front Biosci,2012,17,300-315.
17.Johnsson P,Ackley A,Vidarsdottir L.et al.A pseudogene long-noncoding-RNA network regulates PTEN transcription and translation in human cells[J].Nat.Struct.Mol.Biol,2013,20(4),440-446.
18.Guttman,M.Rinn,J.L.Modular regulatory principles of large non-coding RNAs[J].Nature,2012,482(7 385),339-346.
19.Faust,T.;Frankel,A D’Orso,I.Transcription control by longnon-codingRNAs[J].Transcription,2012;3(2):78-86.
20.Chen,L.L.Carmichael,G.G.Decoding the function of nuclear long non-coding RNAs[J].Curr Opin Cell Biol,2010,22(3):357-364.
21.Bauer EM,Zheng H,Comhair S.et al.Complement C3deficiency attenuates chronic hypoxia-induced pulmonary hypertension in mice[J].PLoS One,2011,6(12):e28 578.
22.Delbeck M,Nickel KF,Perzborn E.et al.A role for coagulation factor Xa in experimental pulmonary arterial hypertension[J].Cardiovasc Res,2011,92(1):159-168.
23.Burstein B,Comtois P,Michael G,et al.Changes in connexin expression and the atrial fibrillation substrate in congestive heart failure[J].Circ Res,2012;105:1 213-1 222.
24.Scott Valastyan,Robert A Weinberg.Roles for microRNAs in the regulation of cell adhesion molecules[J].Cell Sci,2011,124(7):999-1 006.
25.Sudo R,Sato F,Azechi T,et al.MiR-29-mediated elastin down-regulation contributes to inorganic phosphorus-induced osteoblastic differentiation in vascular smooth muscle cells[J].Genes cells,2015,20(12)1 077-1087.
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