Abstract
Diabetes remains one of the most prevalent non-communicable diseases in the world, affecting over 400 million of people worldwide, causing serious complications leading to amputations and even death. Over the years, researchers have found that, in addition to genomic mutations, epigenetic mechanisms also play a role in the development of diabetes-specifically type-2 diabetes. Long noncoding RNAs (lncRNAs) have been linked to mediate epigenetic mechanisms, including those in late-stage diabetes. This study attempts to assess the unexplored topic of how lncRNAs could be used to assess the epigenetic mechanisms present in diabetic peripheral neuropathy (DPN); a serious complication of the disease often leading to amputation. Differential lncRNA expression analysis was done with a dataset containing DPN and healthy patients. Standard and corrected t test, and also LIMMA was applied. Results of this study indicates the usefulness of lncRNAs as an exploratory tool to elucidate the complexity of the epigenetic mechanisms of human DPN.
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References
Al-Haddad R, Karnib N, Assaad RA, Bilen Y, Emmanuel N, Ghanem A et al (2016) Epigenetic changes in diabetes. Neurosci Lett 625:64–69. https://doi.org/10.1016/j.neulet.2016.04.046
Amaral PP, Mattick JS (2008) Noncoding RNA in development. Mamm Genome. https://doi.org/10.1007/s00335-008-9136-7
Belinky F, Bahir I, Stelzer G, Zimmerman S, Rosen N, Nativ N et al (2013) Non-redundant compendium of human ncRNA genes in GeneCards. Bioinform 29(2):255–261. https://doi.org/10.1093/bioinformatics/bts676
Bhat SA, Ahmad SM, Mumtaz PT, Malik AA, Dar MA, Urwat U et al (2016) Long non-coding RNAs: mechanism of action and functional utility. NonCoding RNA Res 1(1):43–50. https://doi.org/10.1016/j.ncrna.2016.11.002
Boulton AJM (2005) Management of diabetic peripheral neuropathy. Clin Diabetes 23(1):9–15
Davis S, Meltzer PS (2007) GEOquery: a bridge between the gene expression omnibus (GEO) and BioConductor. Bioinform 23(14):1846–1847. https://doi.org/10.1093/bioinformatics/btm254
Dean L, McEntyre J (2004) The genetic landscape of diabetes. National Center for Biotechnology Information (US), Bethesda (MD). https://www.ncbi.nlm.nih.gov/books/NBK1667/
Edgar R, Domrachev M, Lash AE (2002) Gene expression omnibus: NCBI gene expression and hybridization array data repository. Nucleic Acids Res 30(1):207–210
Feinberg AP, Fallin MD (2015) Epigenetics at the crossroads of genes and the environment. JAMA 314(11):1129–1130. https://doi.org/10.1001/jama.2015.10414
Grote P, Wittler L, Hendrix D, Koch F, Währisch S, Beisaw A et al (2013) The tissue-specific lncRNA fendrr is an essential regulator of heart and body wall development in the mouse. Dev Cell 24(2):206–214. https://doi.org/10.1016/j.devcel.2012.12.012
Hara K, Shojima N, Hosoe J, Kadowaki T (2014) Genetic architecture of type 2 diabetes. Biochem Biophys Res Commun 452:213–220. https://doi.org/10.1016/j.bbrc.2014.08.012
Huber W, Carey VJ, Gentleman R, Anders S, Carlson M, Carvalho BS et al (2015) Orchestrating high-throughput genomic analysis with Bioconductor. Nat Methods 12(2):115–121. https://doi.org/10.1038/nmeth.3252
Karachanak-Yankova S, Dimova R, Nikolova D, Nesheva D, Koprinarova M, Maslyankov S et al (2015) Epigenetic alterations in patients with type 2 diabetes mellitus. Balkan J Med Genet 18(2):15–24. https://doi.org/10.1515/bjmg-2015-0081
Kolarz B, Majdan M (2017) Epigenetic aspects of rheumatoid arthritis: contribution of non-coding RNAs. Semin Arthritis Rheum. https://doi.org/10.1016/j.semarthrit.2017.01.003
Kornfeld JW, Brüning JC (2014) Regulation of metabolism by long, non-coding RNAs. Front Genet. https://doi.org/10.3389/fgene.2014.00057
Li Q, Su Z, Xu X, Liu G, Song X, Wang R et al (2012) AS1DHRS4, a head-to-head natural antisense transcript, silences the DHRS4 gene cluster in cis and trans. Proc Natl Acad Sci 109(35):14110–14115. https://doi.org/10.1073/pnas.1116597109
Louis DN, Perry A, Burger P, Ellison DW, Reifenberger G, von Deimling A (2014) International society of neuropathology-haarlem consensus guidelines for nervous system tumor classification and grading. Brain Pathol 24(5):429–435. https://doi.org/10.1111/bpa.12171
Lu MC, Yu HC, Yu CL, Huang HB, Koo M, Tung CH, Lai NS (2016) Increased expression of long noncoding RNAs LOC100652951 and LOC100506036 in T cells from patients with rheumatoid arthritis facilitates the inflammatory responses. Immunol Res 64(2):576–583. https://doi.org/10.1007/s12026-015-8756-8
Luo L, Xu J (2017) Transcriptional profiling of diabetic peripheral neuropathy patients, diabetic patients, and healthy participants. J Diabetes Res. https://doi.org/10.1155/2017/8103904
Mattick JS (2005) The functional genomics of noncoding RNA. Science 309(5740):1527–1528. https://doi.org/10.1126/science.1117806
Ota T, Suzuki Y, Nishikawa T, Otsuki T, Sugiyama T, Irie R (2004) Complete sequencing and characterization of 21,243 full-length human cDNAs. Nat Genet 36(1):40–45. https://doi.org/10.1038/ng1285
Parikesit AA, Steiner L, Stadler PF, Prohaska SJ (2014) Pitfalls of ascertainment biases in genome annotations—computing comparable protein domain distributions in Eukarya. Malays J Fundam Appl Sci 10(2):65–75. https://doi.org/10.11113/mjfas.v10n2.57
Prohaska SJ, Stadler PF, Krakauer DC (2010) Innovation in gene regulation: the case of chromatin computation. J Theor Biol 265(1):27–44. https://doi.org/10.1016/j.jtbi.2010.03.011
Pullen TJ, Rutter GA (2014) Roles of lncRNAs in pancreatic beta cell identity and diabetes susceptibility. Front Genet. https://doi.org/10.3389/fgene.2014.00193
Reddy MA, Zhang E, Natarajan R (2015) Epigenetic mechanisms in diabetic complications and metabolic memory. Diabetologia 58(3):443–455. https://doi.org/10.1007/s00125-014-3462-y
Ritchie ME, Phipson B, Wu D, Hu Y, Law CW, Shi W, Smyth GK (2015) limma powers differential expression analyses for RNA-sequencing and microarray studies. Nucleic Acids Res 43(7):e47–e47. https://doi.org/10.1093/nar/gkv007
Rouillard AD, Gundersen GW, Fernandez NF, Wang Z, Monteiro CD, McDermott MG, Ma’ayan A (2016) The harmonizome: a collection of processed datasets gathered to serve and mine knowledge about genes and proteins. Database. https://doi.org/10.1093/database/baw100
RStudio Team (2015) Integrated development for R. RStudio, Inc. R. RStudio, Inc., Boston
Safran M, Dalah I, Alexander J, Rosen N, Iny Stein T, Shmoish M et al (2010) GeneCards Version 3: the human gene integrator. Database J Biol Databases Curation. https://doi.org/10.1093/database/baq020
Steiner L, Hopp L, Wirth H, Galle J, Binder H, Prohaska SJ, Rohlf T (2012) A global genome segmentation method for exploration of epigenetic patterns. PLoS ONE 7(10):e46811. https://doi.org/10.1371/journal.pone.0046811
Stelzer G, Rosen N, Plaschkes I, Zimmerman S, Twik M, Fishilevich S et al (2016) The GeneCards suite: from gene data mining to disease genome sequence analyses. Curr Prot Bioinf. https://doi.org/10.1002/cpbi.5
Swami M (2009) Epigenetics: misreading the code. Nat Publ Group 9:461. https://doi.org/10.1038/nrc2679
World Health Organization (2016a) Global report on diabetes. Isbn, 978, 88. ISBN: 978 92 4 156525 7
World Health Organization (2016b) WHO | diabetes. WHO, Geneva
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Authors thanks to Indonesia International Institute for Life Sciences for facilitated this research.
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Fachrul, M., Utomo, D.H. & Parikesit, A.A. lncRNA-based study of epigenetic regulations in diabetic peripheral neuropathy. In Silico Pharmacol. 6, 7 (2018). https://doi.org/10.1007/s40203-018-0042-8
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DOI: https://doi.org/10.1007/s40203-018-0042-8