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HOTAIR Long Non-coding RNA: Characterizing the Locus Features by the In Silico Approaches

  • Received : 2017.08.04
  • Accepted : 2017.09.18
  • Published : 2017.12.31

Abstract

HOTAIR is an lncRNA that has been known to have an oncogenic role in different cancers. There is limited knowledge of genetic and epigenetic elements and their interactions for the gene encoding HOTAIR. Therefore, understanding the molecular mechanism and its regulation remains to be challenging. We used different in silico analyses to find genetic and epigenetic elements of HOTAIR gene to gain insight into its regulation. We reported different regulatory elements including canonical promoters, transcription start sites, CpGIs as well as epigenetic marks that are potentially involved in the regulation of HOTAIR gene expression. We identified repeat sequences and single nucleotide polymorphisms that are located within or next to the CpGIs of HOTAIR. Our analyses may help to find potential interactions between genetic and epigenetic elements of HOTAIR gene in the human tissues and show opportunities and limitations for researches on HOTAIR gene in future studies.

Keywords

References

  1. Harrow J, Frankish A, Gonzalez JM, Tapanari E, Diekhans M, Kokocinski F, et al. GENCODE: the reference human genome annotation for The ENCODE Project. Genome Res 2012;22:1760-1774. https://doi.org/10.1101/gr.135350.111
  2. Kapranov P, Cheng J, Dike S, Nix DA, Duttagupta R, Willingham AT, et al. RNA maps reveal new RNA classes and a possible function for pervasive transcription. Science 2007;316:1484-1488. https://doi.org/10.1126/science.1138341
  3. Hajjari M, Salavaty A. HOTAIR: an oncogenic long non-coding RNA in different cancers. Cancer Biol Med 2015;12:1-9.
  4. Fatica A, Bozzoni I. Long non-coding RNAs: new players in cell differentiation and development. Nat Rev Genet 2014;15:7-21.
  5. Yu X, Li Z. Long non-coding RNA HOTAIR: a novel oncogene (review). Mol Med Rep 2015;12:5611-5618. https://doi.org/10.3892/mmr.2015.4161
  6. Khandelwal A, Malhotra A, Jain M, Vasquez KM, Jain A. The emerging role of long non-coding RNA in gallbladder cancer pathogenesis. Biochimie 2017;132:152-160. https://doi.org/10.1016/j.biochi.2016.11.007
  7. Rinn JL. lncRNAs: linking RNA to chromatin. Cold Spring Harb Perspect Biol 2014;6:a018614. https://doi.org/10.1101/cshperspect.a018614
  8. Mercer TR, Mattick JS. Structure and function of long noncoding RNAs in epigenetic regulation. Nat Struct Mol Biol 2013;20:300-307. https://doi.org/10.1038/nsmb.2480
  9. Li CH, Chen Y. Targeting long non-coding RNAs in cancers: progress and prospects. Int J Biochem Cell Biol 2013;45:1895-1910. https://doi.org/10.1016/j.biocel.2013.05.030
  10. Ishibashi M, Kogo R, Shibata K, Sawada G, Takahashi Y, Kurashige J, et al. Clinical significance of the expression of long non-coding RNA HOTAIR in primary hepatocellular carcinoma. Oncol Rep 2013;29:946-950. https://doi.org/10.3892/or.2012.2219
  11. Rinn JL, Kertesz M, Wang JK, Squazzo SL, Xu X, Brugmann SA, et al. Functional demarcation of active and silent chromatin domains in human HOX loci by noncoding RNAs. Cell 2007;129:1311-1323. https://doi.org/10.1016/j.cell.2007.05.022
  12. Loewen G, Zhuo Y, Zhuang Y, Jayawickramarajah J, Shan B. lincRNA HOTAIR as a novel promoter of cancer progression. J Can Res Updates 2014;3:134-140. https://doi.org/10.6000/1929-2279.2014.03.03.3
  13. Bhan A, Mandal SS. Estradiol-induced transcriptional regulation of long non-coding RNA, HOTAIR. Methods Mol Biol 2016;1366:395-412.
  14. He S, Liu S, Zhu H. The sequence, structure and evolutionary features of HOTAIR in mammals. BMC Evol Biol 2011;11:102. https://doi.org/10.1186/1471-2148-11-102
  15. Zhang J, Zhang P, Wang L, Piao HL, Ma L. Long non-coding RNA HOTAIR in carcinogenesis and metastasis. Acta Biochim Biophys Sin (Shanghai) 2014;46:1-5. https://doi.org/10.1093/abbs/gmt117
  16. Schorderet P, Duboule D. Structural and functional differences in the long non-coding RNA hotair in mouse and human. PLoS Genet 2011;7:e1002071. https://doi.org/10.1371/journal.pgen.1002071
  17. Tsai MC, Manor O, Wan Y, Mosammaparast N, Wang JK, Lan F, et al. Long noncoding RNA as modular scaffold of histone modification complexes. Science 2010;329:689-693. https://doi.org/10.1126/science.1192002
  18. Meredith EK, Balas MM, Sindy K, Haislop K, Johnson AM. An RNA matchmaker protein regulates the activity of the long noncoding RNA HOTAIR. RNA 2016;22:995-1010. https://doi.org/10.1261/rna.055830.115
  19. Ma MZ, Li CX, Zhang Y, Weng MZ, Zhang MD, Qin YY, et al. Long non-coding RNA HOTAIR, a c-Myc activated driver of malignancy, negatively regulates miRNA-130a in gallbladder cancer. Mol Cancer 2014;13:156. https://doi.org/10.1186/1476-4598-13-156
  20. Wu Y, Zhang L, Wang Y, Li H, Ren X, Wei F, et al. Long noncoding RNA HOTAIR involvement in cancer. Tumour Biol 2014;35:9531-9538. https://doi.org/10.1007/s13277-014-2523-7
  21. Berrondo C, Flax J, Kucherov V, Siebert A, Osinski T, Rosenberg A, et al. Expression of the long non-coding RNA HOTAIR correlates with disease progression in bladder cancer and is contained in bladder cancer patient urinary exosomes. PLoS One 2016;11:e0147236. https://doi.org/10.1371/journal.pone.0147236
  22. Kim HJ, Lee DW, Yim GW, Nam EJ, Kim S, Kim SW, et al. Long non-coding RNA HOTAIR is associated with human cervical cancer progression. Int J Oncol 2015;46:521-530. https://doi.org/10.3892/ijo.2014.2758
  23. Li J, Yang S, Su N, Wang Y, Yu J, Qiu H, et al. Overexpression of long non-coding RNA HOTAIR leads to chemoresistance by activating the Wnt/beta-catenin pathway in human ovarian cancer. Tumour Biol 2016;37:2057-2065. https://doi.org/10.1007/s13277-015-3998-6
  24. Chiyomaru T, Fukuhara S, Saini S, Majid S, Deng G, Shahryari V, et al. Long non-coding RNA HOTAIR is targeted and regulated by miR-141 in human cancer cells. J Biol Chem 2014;289:12550-12565. https://doi.org/10.1074/jbc.M113.488593
  25. Guo W, Dong Z, Bai Y, Guo Y, Shen S, Kuang G, et al. Associations between polymorphisms of HOTAIR and risk of gastric cardia adenocarcinoma in a population of north China. Tumour Biol 2015;36:2845-2854. https://doi.org/10.1007/s13277-014-2912-y
  26. Marino-Ramirez L, Spouge JL, Kanga GC, Landsman D. Statistical analysis of over-represented words in human promoter sequences. Nucleic Acids Res 2004;32:949-958. https://doi.org/10.1093/nar/gkh246
  27. Pedersen AG, Baldi P, Brunak S, Chauvin Y. Characterization of prokaryotic and eukaryotic promoters using hidden Markov models. Proc Int Conf Intell Syst Mol Biol 1996;4:182-191.
  28. Prestridge DS. Predicting Pol II promoter sequences using transcription factor binding sites. J Mol Biol 1995;249:923-932. https://doi.org/10.1006/jmbi.1995.0349
  29. Down TA, Hubbard TJ. Computational detection and location of transcription start sites in mammalian genomic DNA. Genome Res 2002;12:458-461. https://doi.org/10.1101/gr.216102
  30. Gardiner-Garden M, Frommer M. CpG islands in vertebrate genomes. J Mol Biol 1987;196:261-282. https://doi.org/10.1016/0022-2836(87)90689-9
  31. Boucher CA, King SK, Carey N, Krahe R, Winchester CL, Rahman S, et al. A novel homeodomain-encoding gene is associated with a large CpG island interrupted by the myotonic dystrophy unstable (CTG)n repeat. Hum Mol Genet 1995;4:1919-1925. https://doi.org/10.1093/hmg/4.10.1919
  32. Bock C, Walter J, Paulsen M, Lengauer T. CpG island mapping by epigenome prediction. PLoS Comput Biol 2007;3:e110. https://doi.org/10.1371/journal.pcbi.0030110
  33. Hajjari M, Khoshnevisan A, Lemos B. Characterizing the retinoblastoma 1 locus: putative elements for Rb1 regulation by in silico analysis. Front Genet 2014;5:2.
  34. Ponger L, Mouchiroud D. CpGProD: identifying CpG islands associated with transcription start sites in large genomic mammalian sequences. Bioinformatics 2002;18:631-633. https://doi.org/10.1093/bioinformatics/18.4.631
  35. Wang Z, Fan H, Yang HH, Hu Y, Buetow KH, Lee MP. Comparative sequence analysis of imprinted genes between human and mouse to reveal imprinting signatures. Genomics 2004;83:395-401. https://doi.org/10.1016/j.ygeno.2003.09.007
  36. Hajjari M, Behmanesh M, Jahani MM. In silico finding of putative cis-acting elements for the tethering of polycomb repressive complex2 in human genome. Bioinformation 2014;10:187-190. https://doi.org/10.6026/97320630010187
  37. Janssen CS, Phillips RS, Turner CM, Barrett MP. Plasmodium interspersed repeats: the major multigene superfamily of malaria parasites. Nucleic Acids Res 2004;32:5712-5720. https://doi.org/10.1093/nar/gkh907
  38. Jeziorska DM, Jordan KW, Vance KW. A systems biology approach to understanding cis-regulatory module function. Semin Cell Dev Biol 2009;20:856-862. https://doi.org/10.1016/j.semcdb.2009.07.007
  39. Ferretti V, Poitras C, Bergeron D, Coulombe B, Robert F, Blanchette M. PReMod: a database of genome-wide mammalian cis-regulatory module predictions. Nucleic Acids Res 2007;35:D122-D126. https://doi.org/10.1093/nar/gkl879
  40. Benson G. Tandem repeats finder: a program to analyze DNA sequences. Nucleic Acids Res 1999;27:573-580. https://doi.org/10.1093/nar/27.2.573
  41. Suzuki H, Maruyama R, Yamamoto E, Niinuma T, Kai M. Relationship between noncoding RNA dysregulation and epigenetic mechanisms in cancer. In: The Long and Short Non-coding RNAs in Cancer Biology (Song E, ed.). Singapore: Springer, 2016. pp. 109-135.
  42. Deng J, Yang M, Jiang R, An N, Wang X, Liu B. Long non-coding RNA HOTAIR regulates the proliferation, self-renewal capacity, tumor formation and migration of the cancer stem-like cell (CSC) subpopulation enriched from breast cancer cells. PLoS One 2017;12:e0170860. https://doi.org/10.1371/journal.pone.0170860
  43. Kim K, Jutooru I, Chadalapaka G, Johnson G, Frank J, Burghardt R, et al. HOTAIR is a negative prognostic factor and exhibits pro-oncogenic activity in pancreatic cancer. Oncogene 2013;32:1616-1625. https://doi.org/10.1038/onc.2012.193
  44. Nakagawa T, Endo H, Yokoyama M, Abe J, Tamai K, Tanaka N, et al. Large noncoding RNA HOTAIR enhances aggressive biological behavior and is associated with short disease-free survival in human non-small cell lung cancer. Biochem Biophys Res Commun 2013;436:319-324. https://doi.org/10.1016/j.bbrc.2013.05.101
  45. Borley J, Brown R. Epigenetic mechanisms and therapeutic targets of chemotherapy resistance in epithelial ovarian cancer. Ann Med 2015;47:359-369. https://doi.org/10.3109/07853890.2015.1043140
  46. Loewen G, Jayawickramarajah J, Zhuo Y, Shan B. Functions of lncRNA HOTAIR in lung cancer. J Hematol Oncol 2014;7:90. https://doi.org/10.1186/s13045-014-0090-4
  47. Jones PA. Functions of DNA methylation: islands, start sites, gene bodies and beyond. Nat Rev Genet 2012;13:484-492. https://doi.org/10.1038/nrg3230
  48. Pan W, Liu L, Wei J, Ge Y, Zhang J, Chen H, et al. A functional lncRNA HOTAIR genetic variant contributes to gastric cancer susceptibility. Mol Carcinog 2016;55:90-96. https://doi.org/10.1002/mc.22261
  49. Du M, Wang W, Jin H, Wang Q, Ge Y, Lu J, et al. The association analysis of lncRNA HOTAIR genetic variants and gastric cancer risk in a Chinese population. Oncotarget 2015;6:31255-31262.
  50. Xue Y, Gu D, Ma G, Zhu L, Hua Q, Chu H, et al. Genetic variants in lncRNA HOTAIR are associated with risk of colorectal cancer. Mutagenesis 2015;30:303-310. https://doi.org/10.1093/mutage/geu076
  51. Yan R, Cao J, Song C, Chen Y, Wu Z, Wang K, et al. Polymorphisms in lncRNA HOTAIR and susceptibility to breast cancer in a Chinese population. Cancer Epidemiol 2015;39:978-985. https://doi.org/10.1016/j.canep.2015.10.025
  52. Wu H, Shang X, Shi Y, Yang Z, Zhao J, Yang M, et al. Genetic variants of lncRNA HOTAIR and risk of epithelial ovarian cancer among Chinese women. Oncotarget 2016;7:41047-41052.

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