Microarray profiling of long non-coding RNA (lncRNA) associated with hypertrophic cardiomyopathy

BMC Cardiovascular Disorders

Haixiang Wu¹  Fawei He¹  Yuan Li¹  Wei Yang¹ 

[1] Department of Ultrasonics, The Second Hospital of Sichuan, No. 55, People’s South Road, Wuhou District, Chengdu, 610041, Sichuan, China

关键词: KEGG pathway;    Gene ontology;    LncRNA;    Hypertrophic cardiomyopathy;   

Others  :  1217281
DOI  :  10.1186/s12872-015-0056-7

 received in 2014-11-23, accepted in 2015-06-11,  发布年份 2015

【 摘 要 】

Background

Hypertrophic cardiomyopathy (HCM) is an inherited disorder with around 1400 known mutations; however the molecular pathways leading from genotype to phenotype are not fully understood. LncRNAs, which account for approximately 98 % of human genome, are becoming increasingly interesting with regard to various diseases. However, changes in the expression of regulatory lncRNAs in HCM have not yet been reported.

To identify myocardial lncRNAs involved in HCM and characterize their roles in HCM pathogenesis.

Methods

Myocardial tissues were obtained from 7 HCM patients and 5 healthy individuals, and lncRNA and mRNA expression profiles were analyzed using the Arraystar human lncRNA microarray. Real-time PCR was conducted to validate the expression pattern of lncRNA and mRNA. Gene ontology (GO) enrichment and KEGG analysis of mRNAs was conducted to identify the related biological modules and pathologic pathways.

Results

Approximately 1426 lncRNAs (965 up-regulated and 461 down-regulated) and 1715 mRNAs (896 up-regulated and 819 down-regulated) were aberrantly expressed in HCM patients with fold change > 2.0. GO analysis indicated that these lncRNAs–coexpressed mRNAs were targeted to translational process. Pathway analysis indicated that lncRNAs–coexpressed mRNAs were mostly enriched in ribosome and oxidative phosphorylation.

Conclusion

LncRNAs are involved in the pathogenesis of HCM through the modulation of multiple pathogenetic pathways.

【 授权许可】

   
2015 Yang et al.

【 图 表 】

Fig. 1.

Fig. 2.

Fig. 3.

Fig. 4.

Fig. 5.

【 参考文献 】

• [1]Ho CY: Hypertrophic cardiomyopathy in 2012. Circulation 2012, 125(11):1432-8.
• [2]Maron BJ: Hypertrophic cardiomyopathy: an important global disease. Am J Med 2004, 116(1):63-5.
• [3]Maron BJ, Maron MS: Hypertrophic cardiomyopathy. Lancet 2013, 381(9862):242-55.
• [4]Maron BJ: Hypertrophic cardiomyopathy: a systematic review. JAMA 2002, 287(10):1308-20.
• [5]Maron BJ, Thompson PD, Puffer JC, McGrew CA, Strong WB, Douglas PS, Clark LT, Mitten MJ, Crawford MD, Atkins DL, et al.: Cardiovascular preparticipation screening of competitive athletes: addendum: an addendum to a statement for health professionals from the Sudden Death Committee (Council on Clinical Cardiology) and the Congenital Cardiac Defects Committee (Council on Cardiovascular Disease in the Young), American Heart Association. Circulation 1998, 97(22):2294.
• [6]Maron MS, Olivotto I, Betocchi S, Casey SA, Lesser JR, Losi MA, Cecchi F, Maron BJ: Effect of left ventricular outflow tract obstruction on clinical outcome in hypertrophic cardiomyopathy. N Engl J Med 2003, 348(4):295-303.
• [7]Maron BJ, Maron MS, Semsarian C: Genetics of hypertrophic cardiomyopathy after 20 years: clinical perspectives. J Am Coll Cardiol 2012, 60(8):705-15.
• [8]Efthimiadis GK, Pagourelias ED, Gossios T, Zegkos T: Hypertrophic cardiomyopathy in 2013: Current speculations and future perspectives. World J Cardiol 2014, 6(2):26-37.
• [9]Nishimura RA, Ommen SR: Hypertrophic cardiomyopathy: the search for obstruction. Circulation 2006, 114(21):2200-2.
• [10]Roma-Rodrigues C, Fernandes AR: Genetics of hypertrophic cardiomyopathy: advances and pitfalls in molecular diagnosis and therapy. Appl Clin Genet 2014, 7:195-208.
• [11]Guttman M, Amit I, Garber M, French C, Lin MF, Feldser D, Huarte M, Zuk O, Carey BW, Cassady JP, et al.: Chromatin signature reveals over a thousand highly conserved large non-coding RNAs in mammals. Nature 2009, 458(7235):223-7.
• [12]Derrien T, Johnson R, Bussotti G, Tanzer A, Djebali S, Tilgner H, Guernec G, Martin D, Merkel A, Knowles DG, et al.: The GENCODE v7 catalog of human long noncoding RNAs: analysis of their gene structure, evolution, and expression. Genome Res 2012, 22(9):1775-89.
• [13]Mattick JS: The genetic signatures of noncoding RNAs. PLoS Genet 2009., 5(4) Article ID e1000459
• [14]Rinn JL, Chang HY: Genome regulation by long noncoding RNAs. Annu Rev Biochem 2012, 81:145-66.
• [15]Ge X, Chen Y, Liao X, Liu D, Li F, Ruan H, Jia W: Overexpression of long noncoding RNA PCAT-1 is a novel biomarker of poor prognosis in patients with colorectal cancer. Med Oncol 2013, 30(2):588.
• [16]Barry G, Briggs JA, Vanichkina DP, Poth EM, Beveridge NJ, Ratnu VS, Nayler SP, Nones K, Hu J, Bredy TW, et al.: The long non-coding RNA Gomafu is acutely regulated in response to neuronal activation and involved in schizophrenia-associated alternative splicing. Mol Psychiatry 2014, 19(4):486-94.
• [17]Dennis G Jr, Sherman BT, Hosack DA, Yang J, Gao W, Lane HC, Lempicki RA: DAVID: Database for Annotation, Visualization, and Integrated Discovery. Genome Biol 2003, 4(5):3. BioMed Central Full Text
• [18]Ashburner M, Ball CA, Blake JA, Botstein D, Butler H, Cherry JM, Davis AP, Dolinski K, Dwight SS, Eppig JT, et al.: Gene ontology: tool for the unification of biology. The Gene Ontology Consortium. Nat Genet 2000, 25(1):25-9.
• [19]Guttman M, Donaghey J, Carey BW, Garber M, Grenier JK, Munson G, Young G, Lucas AB, Ach R, Bruhn L, et al.: lincRNAs act in the circuitry controlling pluripotency and differentiation. Nature 2011, 477(7364):295-300.
• [20]Lim DS, Roberts R, Marian AJ: Expression profiling of cardiac genes in human hypertrophic cardiomyopathy: insight into the pathogenesis of phenotypes. J Am Coll Cardiol 2001, 38(4):1175-80.
• [21]Wei BR, Simpson RM, Johann DJ, Dwyer JE, Prieto DA, Kumar M, Ye X, Luke B, Shive HR, Webster JD, et al.: Proteomic profiling of H-Ras-G12V induced hypertrophic cardiomyopathy in transgenic mice using comparative LC-MS analysis of thin fresh-frozen tissue sections. J Proteome Res 2012, 11(3):1561-70.
• [22]Lam L, Tsoutsman T, Arthur J, Semsarian C: Differential protein expression profiling of myocardial tissue in a mouse model of hypertrophic cardiomyopathy. J Mol Cell Cardiol 2010, 48(5):1014-22.
• [23]Rajan S, Pena JR, Jegga AG, Aronow BJ, Wolska BM, Wieczorek DF: Microarray analysis of active cardiac remodeling genes in a familial hypertrophic cardiomyopathy mouse model rescued by a phospholamban knockout. Physiol Genomics 2013, 45(17):764-73.
• [24]Gonzalez-Dominguez R, Garcia A, Garcia-Barrera T, Barbas C, Gomez-Ariza JL: Metabolomic profiling of serum in the progression of Alzheimer’s disease by capillary electrophoresis-mass spectrometry. Electrophoresis 2014, 35(23):3321-30.
• [25]Fan Y, Wei C, Xiao W, Zhang W, Wang N, Chuang PY, He JC: Temporal profile of the renal transcriptome of HIV-1 transgenic mice during disease progression. PLoS One 2014., 9(3) Article ID e93019
• [26]Bauer M, Gramlich I, Polzin S, Patzelt D: Quantification of mRNA degradation as possible indicator of postmortem interval–a pilot study. Leg Med 2003, 5(4):220-7.
• [27]Young ST, Wells JD, Hobbs GR, Bishop CP: Estimating postmortem interval using RNA degradation and morphological changes in tooth pulp. Forensic Sci Int 2013, 229(1–3):163.e1-6.
• [28]Spizzo R, Almeida MI, Colombatti A, Calin GA: Long non-coding RNAs and cancer: a new frontier of translational research? Oncogene 2012, 31(43):4577-87.
• [29]Gibb EA, Vucic EA, Enfield KS, Stewart GL, Lonergan KM, Kennett JY, Becker-Santos DD, MacAulay CE, Lam S, Brown CJ, et al.: Human cancer long non-coding RNA transcriptomes. PLoS One 2011., 6(10) Article ID e25915
• [30]Liu Z, Li X, Sun N, Xu Y, Meng Y, Yang C, Wang Y, Zhang K: Microarray profiling and co-expression network analysis of circulating lncRNAs and mRNAs associated with major depressive disorder. PLoS One 2014., 9(3) Article ID e93388
• [31]Han P, Li W, Lin CH, Yang J, Shang C, Nurnberg ST, Jin KK, Xu W, Lin CY, Lin CJ, et al.: A long noncoding RNA protects the heart from pathological hypertrophy. Nature 2014, 514(7520):102-6.
• [32]Liu J, Wang DZ: An epigenetic “LINK(RNA)” to pathological cardiac hypertrophy. Cell Metab 2014, 20(4):555-7.
• [33]Gonzalez C, Sims JS, Hornstein N, Mela A, Garcia F, Lei L, Gass DA, Amendolara B, Bruce JN, Canoll P, et al.: Ribosome profiling reveals a cell-type-specific translational landscape in brain tumors. J Neurosci 2014, 34(33):10924-36.
• [34]Boczonadi V, Horvath R: Mitochondria: impaired mitochondrial translation in human disease. Int J Biochem Cell Biol 2014, 48:77-84.
• [35]Watson PA, Reusch JE, McCune SA, Leinwand LA, Luckey SW, Konhilas JP, Brown DA, Chicco AJ, Sparagna GC, Long CS, et al.: Restoration of CREB function is linked to completion and stabilization of adaptive cardiac hypertrophy in response to exercise. Am J Physiol Heart Circ Physiol 2007, 293(1):H246-59.