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Characterizing miRNA–lncRNA Interplay

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Book cover Long Non-Coding RNAs

Part of the book series: Methods in Molecular Biology ((MIMB,volume 2372))

Abstract

Long noncoding RNAs (lncRNAs) are noncoding transcripts, usually longer than 200 nt, that constitute one of the largest and significantly heterogeneous RNA families. The annotation of lncRNAs and the characterization of their function is a constantly evolving field. LncRNA interplay with microRNAs (miRNAs) is thoroughly studied in several physiological and disease states. miRNAs are small noncoding RNAs (~22 nt) that posttranscriptionally regulate the expression of protein coding genes, through mRNA target cleavage, degradation or direct translational suppression. miRNAs can affect lncRNA half-life by promoting their degradation, or lncRNAs can act as miRNA “sponges,” reducing miRNA regulatory effect on target mRNAs. This chapter outlines the miRNA–lncRNA interplay and provides hands-on methodologies for experimentally supported and in silico-guided analyses. The proposed techniques are a valuable asset to further understand lncRNA functions and can be appropriately adapted to become the backbone for further downstream analyses.

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Abbreviations

ceRNA:

Competing endogenous RNA

CLIP:

Cross-linking immunoprecipitation

lncRNA:

Long noncoding RNA

miRNA:

microRNA

MRE:

miRNA recognition element

References

  1. Cech TR, Steitz JA (2014) The noncoding RNA revolution-trashing old rules to forge new ones. Cell 157(1):77–94

    Article  CAS  PubMed  Google Scholar 

  2. Huntzinger E, Izaurralde E (2011) Gene silencing by microRNAs: contributions of translational repression and mRNA decay. Nat Rev Genet 12(2):99–110

    Article  CAS  PubMed  Google Scholar 

  3. Catalanotto C, Cogoni C, Zardo G (2016) MicroRNA in control of gene expression: an overview of nuclear functions. Int J Mol Sci:17(10)

    Google Scholar 

  4. Derrien T et al (2012) The GENCODE v7 catalog of human long noncoding RNAs: analysis of their gene structure, evolution, and expression. Genome Res 22(9):1775–1789

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Carlevaro-Fita J, Johnson R (2019) Global positioning system: understanding long noncoding RNAs through subcellular localization. Mol Cell 73(5):869–883

    Article  CAS  PubMed  Google Scholar 

  6. Matsumoto A et al (2017) mTORC1 and muscle regeneration are regulated by the LINC00961-encoded SPAR polypeptide. Nature 541(7636):228–232

    Article  CAS  PubMed  Google Scholar 

  7. Li J, Liu C (2019) Coding or noncoding, the converging concepts of RNAs. Front Genet 10:496

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Yao RW, Wang Y, Chen LL (2019) Cellular functions of long noncoding RNAs. Nat Cell Biol 21(5):542–551

    Article  CAS  PubMed  Google Scholar 

  9. Gil N, Ulitsky I (2020) Regulation of gene expression by cis-acting long non-coding RNAs. Nat Rev Genet 21(2):102–117

    Article  CAS  PubMed  Google Scholar 

  10. Vance KW, Ponting CP (2014) Transcriptional regulatory functions of nuclear long noncoding RNAs. Trends Genet 30(8):348–355

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Marchese FP, Raimondi I, Huarte M (2017) The multidimensional mechanisms of long noncoding RNA function. Genome Biol 18(1):206

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  12. Riva P, Ratti A, Venturin M (2016) The long non-coding RNAs in neurodegenerative diseases: novel mechanisms of pathogenesis. Curr Alzheimer Res 13(11):1219–1231

    Article  CAS  PubMed  Google Scholar 

  13. Cai X, Cullen BR (2007) The imprinted H19 noncoding RNA is a primary microRNA precursor. RNA 13(3):313–316

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Dhir A et al (2015) Microprocessor mediates transcriptional termination of long noncoding RNA transcripts hosting microRNAs. Nat Struct Mol Biol 22(4):319–327

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Wang X et al (2015) Silencing of long noncoding RNA MALAT1 by miR-101 and miR-217 inhibits proliferation, migration, and invasion of esophageal squamous cell carcinoma cells. J Biol Chem 290(7):3925–3935

    Article  CAS  PubMed  Google Scholar 

  16. Yoon JH et al (2012) LincRNA-p21 suppresses target mRNA translation. Mol Cell 47(4):648–655

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Cesana M et al (2011) A long noncoding RNA controls muscle differentiation by functioning as a competing endogenous RNA. Cell 147(2):358–369

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Kallen AN et al (2013) The imprinted H19 lncRNA antagonizes let-7 microRNAs. Mol Cell 52(1):101–112

    Article  CAS  PubMed  Google Scholar 

  19. Fuchs Wightman F et al (2018) Target RNAs strike back on MicroRNAs. Front Genet 9:435

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  20. Kleaveland B et al (2018) A network of noncoding regulatory RNAs acts in the mammalian brain. Cell 174(2):350–362.e17

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Faghihi MA et al (2010) Evidence for natural antisense transcript-mediated inhibition of microRNA function. Genome Biol 11(5):R56

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  22. Sun Y et al (2017) A long non-coding RNA HOTTIP expression is associated with disease progression and predicts outcome in small cell lung cancer patients. Mol Cancer 16(1):162

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  23. Karagkouni D et al (2020) DIANA-LncBase v3: indexing experimentally supported miRNA targets on non-coding transcripts. Nucleic Acids Res 48(D1):D101–D110

    CAS  PubMed  Google Scholar 

  24. Huo Y et al (2017) MALAT1 predicts poor survival in osteosarcoma patients and promotes cell metastasis through associating with EZH2. Oncotarget 8(29):46993–47006

    Article  PubMed  PubMed Central  Google Scholar 

  25. Li Y et al (2017) Long non-coding RNA MALAT1 promotes gastric cancer tumorigenicity and metastasis by regulating vasculogenic mimicry and angiogenesis. Cancer Lett 395:31–44

    Article  CAS  PubMed  Google Scholar 

  26. Leucci E et al (2013) microRNA-9 targets the long non-coding RNA MALAT1 for degradation in the nucleus. Sci Rep 3:2535

    Article  PubMed  PubMed Central  Google Scholar 

  27. Song P et al (2016) Long non-coding RNA XIST exerts oncogenic functions in human nasopharyngeal carcinoma by targeting miR-34a-5p. Gene 592(1):8–14

    Article  CAS  PubMed  Google Scholar 

  28. Du Y et al (2017) LncRNA XIST acts as a tumor suppressor in prostate cancer through sponging miR-23a to modulate RKIP expression. Oncotarget 8(55):94358–94370

    Article  PubMed  PubMed Central  Google Scholar 

  29. Liang L et al (2018) LncRNA HCP5 promotes follicular thyroid carcinoma progression via miRNAs sponge. Cell Death Dis 9(3):372

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  30. Wang T et al (2014) Hsa-miR-1 downregulates long non-coding RNA urothelial cancer associated 1 in bladder cancer. Tumour Biol 35(10):10075–10084

    Article  CAS  PubMed  Google Scholar 

  31. Yizhak K et al (2019) RNA sequence analysis reveals macroscopic somatic clonal expansion across normal tissues. Science:364(6444)

    Google Scholar 

  32. Shan Y et al (2018) LncRNA SNHG7 sponges miR-216b to promote proliferation and liver metastasis of colorectal cancer through upregulating GALNT1. Cell Death Dis 9(7):722

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  33. Xu M et al (2018) The long noncoding RNA SNHG1 regulates colorectal cancer cell growth through interactions with EZH2 and miR-154-5p. Mol Cancer 17(1):141

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  34. Xu M et al (2019) lncRNA SNHG6 regulates EZH2 expression by sponging miR-26a/b and miR-214 in colorectal cancer. J Hematol Oncol 12(1):3

    Article  PubMed  PubMed Central  Google Scholar 

  35. Sha M et al (2018) Long non-coding RNA MIAT promotes gastric cancer growth and metastasis through regulation of miR-141/DDX5 pathway. J Exp Clin Cancer Res 37(1):58

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  36. Liu L et al (2019) The long non-coding RNA SNHG1 promotes glioma progression by competitively binding to miR-194 to regulate PHLDA1 expression. Cell Death Dis 10(6):463

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  37. Yao Y et al (2015) Knockdown of long non-coding RNA XIST exerts tumor-suppressive functions in human glioblastoma stem cells by up-regulating miR-152. Cancer Lett 359(1):75–86

    Article  CAS  PubMed  Google Scholar 

  38. Wang Y et al (2018) Long non-coding RNA DSCR8 acts as a molecular sponge for miR-485-5p to activate Wnt/beta-catenin signal pathway in hepatocellular carcinoma. Cell Death Dis 9(9):851

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  39. Tsang FH et al (2015) Long non-coding RNA HOTTIP is frequently up-regulated in hepatocellular carcinoma and is targeted by tumour suppressive miR-125b. Liver Int 35(5):1597–1606

    Article  CAS  PubMed  Google Scholar 

  40. Zhao B et al (2019) MiRNA-124 inhibits the proliferation, migration and invasion of cancer cell in hepatocellular carcinoma by downregulating lncRNA-UCA1. Onco Targets Ther 12:4509–4516

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Li F et al (2019) MALAT1 regulates miR-34a expression in melanoma cells. Cell Death Dis 10(6):389

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Tao F et al (2018) miR-211 sponges lncRNA MALAT1 to suppress tumor growth and progression through inhibiting PHF19 in ovarian carcinoma. FASEB J:fj201800495RR

    Google Scholar 

  43. Tate JG et al (2019) COSMIC: the catalogue of somatic mutations in cancer. Nucleic Acids Res 47(D1):D941–D947

    Article  CAS  PubMed  Google Scholar 

  44. Zhang J et al (2019) STAT3-induced upregulation of lncRNA MEG3 regulates the growth of cardiac hypertrophy through miR-361-5p/HDAC9 axis. Sci Rep 9(1):460

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  45. Liu W et al (2017) Long non-coding RNA MALAT1 contributes to cell apoptosis by sponging miR-124 in Parkinson disease. Cell Biosci 7:19

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  46. Fan Y et al (2020) LncRNA BDNF-AS promotes autophagy and apoptosis in MPTP-induced Parkinson’s disease via ablating microRNA-125b-5p. Brain Res Bull 157:119–127

    Article  CAS  PubMed  Google Scholar 

  47. Cao DW et al (2020) The lncRNA Malat1 functions as a ceRNA to contribute to berberine-mediated inhibition of HMGB1 by sponging miR-181c-5p in poststroke inflammation. Acta Pharmacol Sin 41(1):22–33

    Article  CAS  PubMed  Google Scholar 

  48. Zhong Y, Yu C, Qin W (2019) LncRNA SNHG14 promotes inflammatory response induced by cerebral ischemia/reperfusion injury through regulating miR-136-5p/ROCK1. Cancer Gene Ther 26(7-8):234–247

    Article  CAS  PubMed  Google Scholar 

  49. Zhang L et al (2019) LncRNA Riken-201 and Riken-203 modulates neural development by regulating the Sox6 through sequestering miRNAs. Cell Prolif 52(3):e12573

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  50. Weng R et al (2018) Long noncoding RNA-1604 orchestrates neural differentiation through the miR-200c/ZEB axis. Stem Cells 36(3):325–336

    Article  CAS  PubMed  Google Scholar 

  51. Rani N et al (2016) A primate lncRNA mediates notch signaling during neuronal development by sequestering miRNA. Neuron 90(6):1174–1188

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Li Z et al (2019) LncRNA H19 promotes the committed differentiation of stem cells from apical papilla via miR-141/SPAG9 pathway. Cell Death Dis 10(2):130

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  53. Xu H et al (2019) Inducible degradation of lncRNA Sros1 promotes IFN-gamma-mediated activation of innate immune responses by stabilizing Stat1 mRNA. Nat Immunol 20(12):1621–1630

    Article  CAS  PubMed  Google Scholar 

  54. Karagkouni D et al (2018) DIANA-TarBase v8: a decade-long collection of experimentally supported miRNA-gene interactions. Nucleic Acids Res 46(D1):D239–D245

    Article  CAS  PubMed  Google Scholar 

  55. Andachi Y (2008) A novel biochemical method to identify target genes of individual microRNAs: identification of a new Caenorhabditis elegans let-7 target. RNA 14(11):2440–2451

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Hansen TB et al (2013) Natural RNA circles function as efficient microRNA sponges. Nature 495(7441):384–388

    Article  CAS  PubMed  Google Scholar 

  57. Chi SW et al (2009) Argonaute HITS-CLIP decodes microRNA-mRNA interaction maps. Nature 460(7254):479–486

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Hafner M et al (2010) Transcriptome-wide identification of RNA-binding protein and microRNA target sites by PAR-CLIP. Cell 141(1):129–141

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. Helwak A et al (2013) Mapping the human miRNA interactome by CLASH reveals frequent noncanonical binding. Cell 153(3):654–665

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Frankish A et al (2019) GENCODE reference annotation for the human and mouse genomes. Nucleic Acids Res 47(D1):D766–D773

    Article  CAS  PubMed  Google Scholar 

  61. O’Leary NA et al (2016) Reference sequence (RefSeq) database at NCBI: current status, taxonomic expansion, and functional annotation. Nucleic Acids Res 44(D1):D733–D745

    Article  PubMed  CAS  Google Scholar 

  62. Cabili MN et al (2011) Integrative annotation of human large intergenic noncoding RNAs reveals global properties and specific subclasses. Genes Dev 25(18):1915–1927

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Sherry ST et al (2001) dbSNP: the NCBI database of genetic variation. Nucleic Acids Res 29(1):308–311

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. Landrum MJ et al (2018) ClinVar: improving access to variant interpretations and supporting evidence. Nucleic Acids Res 46(D1):D1062–D1067

    Article  CAS  PubMed  Google Scholar 

  65. Paraskevopoulou MD et al (2018) microCLIP super learning framework uncovers functional transcriptome-wide miRNA interactions. Nat Commun 9(1):3601

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  66. Andrews S, FastQC A (2010) A quality control tool for high throughput sequence data. Google Scholar, 2015

    Google Scholar 

  67. Bolger AM, Lohse M, Usadel B (2014) Trimmomatic: a flexible trimmer for Illumina sequence data. Bioinformatics 30(15):2114–2120

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  68. Wu TD, Nacu S (2010) Fast and SNP-tolerant detection of complex variants and splicing in short reads. Bioinformatics 26(7):873–881

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. Paraskevopoulou MD et al (2013) DIANA-microT web server v5.0: service integration into miRNA functional analysis workflows. Nucleic Acids Res 41(Web Server issue):W169–W173

    Article  PubMed  PubMed Central  Google Scholar 

  70. Paraskevopoulou MD et al (2016) DIANA-LncBase v2: indexing microRNA targets on non-coding transcripts. Nucleic Acids Res 44(D1):D231–D238

    Article  CAS  PubMed  Google Scholar 

  71. Vlachos IS et al (2015) DIANA-miRPath v3.0: deciphering microRNA function with experimental support. Nucleic Acids Res 43(W1):W460–W466

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  72. Gorodkin J, Seemann ES (2019) RNAcentral: a hub of information for non-coding RNA sequences. Nucleic Acids Res 47(D1):D1250–D1251

    Article  Google Scholar 

  73. Kozomara A, Birgaoanu M, Griffiths-Jones S (2019) miRBase: from microRNA sequences to function. Nucleic Acids Res 47(D1):D155–D162

    Article  CAS  PubMed  Google Scholar 

  74. Haeussler M et al (2019) The UCSC Genome Browser database: 2019 update. Nucleic Acids Res 47(D1):D853–D858

    Article  CAS  PubMed  Google Scholar 

  75. Cunningham F et al (2019) Ensembl 2019. Nucleic Acids Res 47(D1):D745–D751

    Article  CAS  PubMed  Google Scholar 

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Acknowledgments

We acknowledge support of this work by the project “ELIXIR-GR: The Greek Research Infrastructure for Data Management and Analysis in Life Sciences” (MIS 5002780) which is implemented under the Action “Reinforcement of the Research and Innovation Infrastructure,” funded by the Operational Programme “Competitiveness, Entrepreneurship and Innovation” (NSRF 2014–2020) and cofinanced by Greece and the European Union (European Regional Development Fund).

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Authors and Affiliations

  1. DIANA-Lab, Department of Computer Science and Biomedical Informatics, University of Thessaly, Lamia, Greece

    Dimitra Karagkouni, Anna Karavangeli, Maria D. Paraskevopoulou & Artemis G. Hatzigeorgiou

  2. Hellenic Pasteur Institute, Athens, Greece

    Dimitra Karagkouni, Anna Karavangeli & Artemis G. Hatzigeorgiou

Authors
  1. Dimitra Karagkouni
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  2. Anna Karavangeli
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  3. Maria D. Paraskevopoulou
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  4. Artemis G. Hatzigeorgiou
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Corresponding authors

Correspondence to Dimitra Karagkouni or Artemis G. Hatzigeorgiou .

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Editors and Affiliations

  1. Department of Obstetrics and Gynecology, University of Pennsylvania, Philadelphia, PA, USA

    Lin Zhang

  2. Department of Obstetrics and Gynecology, University of Pennsylvania, Philadelphia, PA, USA

    Xiaowen Hu

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Karagkouni, D., Karavangeli, A., Paraskevopoulou, M.D., Hatzigeorgiou, A.G. (2021). Characterizing miRNA–lncRNA Interplay. In: Zhang, L., Hu, X. (eds) Long Non-Coding RNAs. Methods in Molecular Biology, vol 2372. Humana, New York, NY. https://doi.org/10.1007/978-1-0716-1697-0_21

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  • DOI: https://doi.org/10.1007/978-1-0716-1697-0_21

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  • Publisher Name: Humana, New York, NY

  • Print ISBN: 978-1-0716-1696-3

  • Online ISBN: 978-1-0716-1697-0

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