Involvement of miRNAs and Pseudogenes in Cancer

  • Lütfi Tutar
  • Aykut Özgür
  • Yusuf TutarEmail author
Part of the Methods in Molecular Biology book series (MIMB, volume 1699)


Our understanding of cancer pathways has been changed by the determination of noncoding transcripts in the human genome in recent years. miRNAs and pseudogenes are key players of the noncoding transcripts from the genome, and alteration of their expression levels provides clues for significant biomarkers in pathogenesis of diseases. Especially, miRNAs and pseudogenes have both oncogenic and tumor-suppressive roles in each step of cancer tumorigenesis. In this current study, association between oncogenes and miRNAs-pseudogenes was reviewed and determined in human cancer by the CellMiner web-tool.

Key words

miRNA Pseudogene Cancer Biomarker CellMiner 


Conflict of Interest

The authors confirm that this article content has no conflicts of interest.


  1. 1.
    Tutar L, Tutar E, Tutar Y (2014) MicroRNAs and cancer; an overview. Curr Pharm Biotechnol 15(5):430–437CrossRefPubMedGoogle Scholar
  2. 2.
    Qu J, Li M, Zhong W, Hu C (2015) Competing endogenous RNA in cancer: a new pattern of gene expression regulation. Int J Clin Exp Med 8(10):17110–17116PubMedPubMedCentralGoogle Scholar
  3. 3.
    Poliseno L, Marranci A, Pandolfi PP (2015) Pseudogenes in human cancer. Front Med 2:68CrossRefGoogle Scholar
  4. 4.
    Garzon R, Calin GA, Croce CM (2009) MicroRNAs in cancer. Annu Rev Med 60:167–179CrossRefPubMedGoogle Scholar
  5. 5.
    Schoof CRG, da Silva Botelho EL, Izzotti A, dos Reis Vasques L (2012) MicroRNAs in cancer treatment and prognosis. Am J Cancer Res 2(4):414–433PubMedPubMedCentralGoogle Scholar
  6. 6.
    Krol J, Loedige I, Filipowicz W (2010) The widespread regulation of microRNA biogenesis, function and decay. Nat Rev Genet 11(9):597–610PubMedGoogle Scholar
  7. 7.
    Tutar Y, Özgür A, Tutar E, Tutar L, Pulliero A et al (2016) Regulation of oncogenic genes by MicroRNAs and pseudogenes in human lung cancer. Biomed Pharmacother 83:1182–1190CrossRefPubMedGoogle Scholar
  8. 8.
    Goodhead I, Darby AC (2015) Taking the pseudo out of pseudogenes. Curr Opin Microbiol 23:102–109CrossRefPubMedGoogle Scholar
  9. 9.
    Tutar Y (2012) Pseudogenes. Comp Funct Genomics 2012:6–9CrossRefGoogle Scholar
  10. 10.
    Korrodi-Gregório L, Abrantes J, Muller T, Melo-Ferreira J, Marcus K et al (2013) Not so pseudo: the evolutionary history of protein phosphatase 1 regulatory subunit 2 and related pseudogenes. BMC Evol Biol 13(1):242CrossRefPubMedPubMedCentralGoogle Scholar
  11. 11.
    Pink RC, Wicks K, Caley DP, Punch EK, Jacobs L et al (2011) Pseudogenes: pseudo-functional or key regulators in health and disease? RNA 17(5):792–798CrossRefPubMedPubMedCentralGoogle Scholar
  12. 12.
    Poliseno L (2012) Pseudogenes: newly discovered players in human cancer. Sci Signal 5(242):re5CrossRefPubMedGoogle Scholar
  13. 13.
    Dweep H, Sticht C, Gretz N (2013) In-Silico algorithms for the screening of possible microRNA binding sites and their interactions. Curr Genomics 14(2):127–136CrossRefPubMedPubMedCentralGoogle Scholar
  14. 14.
    Shankavaram UT, Varma S, Kane D, Sunshine M, Chary KK et al (2009) CellMiner: a relational database and query tool for the NCI-60 cancer cell lines. BMC Genomics 10:277CrossRefPubMedPubMedCentralGoogle Scholar
  15. 15.
    Özgür A, Tutar L, Tutar Y (2014) Regulation of heat shock proteins by miRNAs in human breast cancer. Microrna 3(2):118–135CrossRefPubMedGoogle Scholar
  16. 16.
    Baev V, Milev I, Naydenov M, Vachev T, Apostolova E et al (2014) Insight into small RNA abundance and expression in high- and low-temperature stress response using deep sequencing in Arabidopsis. Plant Physiol Biochem 84:105–114CrossRefPubMedGoogle Scholar
  17. 17.
    Ribeiro AO, Schoof CRG, Izzotti A, Pereira LV, Vasques LR (2014) MicroRNAs: modulators of cell identity, and their applications in tissue engineering. Microrna 3(1):45–53CrossRefPubMedPubMedCentralGoogle Scholar
  18. 18.
    Poliseno L, Salmena L, Zhang J, Carver B, Haveman WJ et al (2010) A coding-independent function of gene and pseudogene mRNAs regulates tumour biology. Nature 465(7301):1033–1038CrossRefPubMedPubMedCentralGoogle Scholar
  19. 19.
    Chen C (2005) Real-time quantification of microRNAs by stem-loop RT-PCR. Nucleic Acids Res 33(20):e179CrossRefPubMedPubMedCentralGoogle Scholar
  20. 20.
    Volinia S, Calin GA, Liu C-G, Ambs S, Cimmino A et al (2006) A microRNA expression signature of human solid tumors defines cancer gene targets. Proc Natl Acad Sci U S A 103(7):2257–2261CrossRefPubMedPubMedCentralGoogle Scholar
  21. 21.
    Lu J, Getz G, Miska EA, Alvarez-Saavedra E, Lamb J et al (2005) MicroRNA expression profiles classify human cancers. Nature 435(7043):834–838CrossRefPubMedGoogle Scholar
  22. 22.
    Hui ABY, Shi W, Boutros PC, Miller N, Pintilie M et al (2009) Robust global micro-RNA profiling with formalin-fixed paraffin-embedded breast cancer tissues. Lab Invest 89(5):597–606CrossRefPubMedGoogle Scholar
  23. 23.
    Weber JA, Baxter DH, Zhang S, Huang DY, Huang KH et al (2010) The microRNA spectrum in 12 body fluids. Clin Chem 56(11):1733–1741CrossRefPubMedPubMedCentralGoogle Scholar
  24. 24.
    Gumireddy K, Young DD, Xiong X, Hogenesch JB, Huang Q et al (2008) Small-molecule inhibitors of microRNA miR-21 function. Angew Chem Int Ed Engl 47(39):7482–7484CrossRefPubMedPubMedCentralGoogle Scholar
  25. 25.
    Bader AG, Brown D, Winkler M (2010) The promise of microRNA replacement therapy. Cancer Res 70(18):7027–7030CrossRefPubMedPubMedCentralGoogle Scholar
  26. 26.
    Calin GA, Dumitru CD, Shimizu M, Bichi R, Zupo S et al (2002) Frequent deletions and down-regulation of micro- RNA genes miR15 and miR16 at 13q14 in chronic lymphocytic leukemia. Proc Natl Acad Sci U S A 99(24):15524–15529CrossRefPubMedPubMedCentralGoogle Scholar
  27. 27.
    Johnson SM, Grosshans H, Shingara J, Byrom M, Jarvis R et al (2005) RAS is regulated by the let-7 microRNA family. Cell 120(5):635–647CrossRefPubMedGoogle Scholar
  28. 28.
    Yong SL, Dutta A (2007) The tumor suppressor microRNA let-7 represses the HMGA2 oncogene. Genes Dev 21(9):1025–1030CrossRefGoogle Scholar
  29. 29.
    Sampson VB, Rong NH, Han J, Yang Q, Aris V et al (2007) MicroRNA let-7a down-regulates MYC and reverts MYC-induced growth in Burkitt lymphoma cells. Cancer Res 67(20):9762–9770CrossRefPubMedGoogle Scholar
  30. 30.
    Muïler D, Bosserhoff A-K (2008) Integrin b 3 expression is regulated by let-7a miRNA in malignant melanoma. Oncogene 27282:6698–6706CrossRefGoogle Scholar
  31. 31.
    Boyerinas B, Park SM, Shomron N, Hedegaard MM, Vinther J et al (2008) Identification of let-7-regulated oncofetal genes. Cancer Res 68(8):2587–2591CrossRefPubMedGoogle Scholar
  32. 32.
    Forman JJ, Legesse-Miller A, Coller HA (2008) A search for conserved sequences in coding regions reveals that the let-7 microRNA targets dicer within its coding sequence. Proc Natl Acad Sci U S A 105(39):14879–14884CrossRefPubMedPubMedCentralGoogle Scholar
  33. 33.
    Toyota M, Suzuki H, Sasaki Y, Maruyama R, Imai K et al (2008) Epigenetic silencing of microRNA-34b/c and B-cell translocation gene 4 is associated with CpG island methylation in colorectal cancer. Cancer Res 68(11):4123–4132CrossRefPubMedGoogle Scholar
  34. 34.
    Michael MZ, O’Connor SM, van Holst Pellekaan NG, Young GP, James RJ (2003) Reduced accumulation of specific microRNAs in colorectal neoplasia. Mol Cancer Res 1(12):882–891PubMedGoogle Scholar
  35. 35.
    Volinia S, Galasso M, Costinean S, Tagliavini L, Gamberoni G et al (2010) Reprogramming of miRNA networks in cancer and leukemia. Genome Res 20(5):589–599CrossRefPubMedPubMedCentralGoogle Scholar
  36. 36.
    Calin GA, Ferracin M, Cimmino A, Di Leva G, Shimizu M et al (2005) A MicroRNA signature associated with prognosis and progression in chronic lymphocytic leukemia. N Engl J Med 353(17):1793–1801CrossRefPubMedGoogle Scholar
  37. 37.
    Garzon R, Volinia S, Liu C, Fernandez-cymering C, Palumbo T et al (2008) MicroRNA signatures associated with cytogenetics and prognosis in acute myeloid leukemia MicroRNA signatures associated with cytogenetics and prognosis in acute myeloid leukemia. Blood 111(6):3183–3189CrossRefPubMedPubMedCentralGoogle Scholar
  38. 38.
    Garzon R, Garofalo M, Martelli MP, Briesewitz R, Wang L et al (2008) Distinctive microRNA signature of acute myeloid leukemia bearing cytoplasmic mutated nucleophosmin. Proc Natl Acad Sci U S A 105(10):3945–3950CrossRefPubMedPubMedCentralGoogle Scholar
  39. 39.
    Ciafrè SA, Galardi S, Mangiola A, Ferracin M, Liu CG et al (2005) Extensive modulation of a set of microRNAs in primary glioblastoma. Biochem Biophys Res Commun 334(4):1351–1358CrossRefPubMedGoogle Scholar
  40. 40.
    Chan JA, Krichevsky AM, Kosik KS (2005) MicroRNA-21 is an antiapoptotic factor in human glioblastoma cells. Cancer Res 65(14):6029–6033CrossRefPubMedGoogle Scholar
  41. 41.
    Meng F, Henson R, Wehbe–Janek H, Ghoshal K, Jacob ST et al (2007) MicroRNA-21 regulates expression of the PTEN tumor suppressor gene in human hepatocellular cancer. Gastroenterology 133(2):647–658CrossRefPubMedPubMedCentralGoogle Scholar
  42. 42.
    Frankel LB, Christoffersen NR, Jacobsen A, Lindow M, Krogh A et al (2008) Programmed cell death 4 (PDCD4) is an important functional target of the microRNA miR-21 in breast cancer cells. J Biol Chem 283(2):1026–1033CrossRefPubMedGoogle Scholar
  43. 43.
    Zhu S, Si ML, Wu H, Mo YY (2007) MicroRNA-21 targets the tumor suppressor gene tropomyosin 1 (TPM1). J Biol Chem 282(19):14328–14336CrossRefPubMedGoogle Scholar
  44. 44.
    Mendell JT (2008) miRiad roles for the miR-17-92 cluster in development and disease. Cell 133(2):217–222CrossRefPubMedPubMedCentralGoogle Scholar
  45. 45.
    O’Donnell KA, Wentzel EA, Zeller KI, Dang CV, Mendell JT (2005) c-Myc-regulated microRNAs modulate E2F1 expression. Nature 435(7043):839–843CrossRefPubMedGoogle Scholar
  46. 46.
    Iorio MV, Ferracin M, Liu CG, Veronese A, Spizzo R et al (2005) MicroRNA gene expression deregulation in human breast cancer. Cancer Res 65(16):7065–7070CrossRefPubMedGoogle Scholar
  47. 47.
    Metzler M, Wilda M, Busch K, Viehmann S, Borkhardt A (2004) High expression of precursor MicroRNA-155/BIC RNA in children with Burkitt lymphoma. Genes Chromosomes Cancer 39(2):167–169CrossRefPubMedGoogle Scholar
  48. 48.
    He H, Jazdzewski K, Li W, Liyanarachchi S, Nagy R et al (2005) The role of microRNA genes in papillary thyroid carcinoma. Proc Natl Acad Sci U S A 102(52):19075–19080CrossRefPubMedPubMedCentralGoogle Scholar
  49. 49.
    Takamizawa J, Konishi H, Yanagisawa K, Tomida S, Osada H et al (2004) Reduced expression of the let-7 microRNAs in human lung cancers in association with shortened postoperative survival. Cancer Res 64(11):3753–3756CrossRefPubMedGoogle Scholar
  50. 50.
    Hayashita Y, Osada H, Tatematsu Y, Yamada H, Yanagisawa K et al (2005) A polycistronic MicroRNA cluster, miR-17-92, is overexpressed in human lung cancers and enhances cell proliferation. Cancer Res 65(21):9628–9632CrossRefPubMedGoogle Scholar
  51. 51.
    Murakami Y, Yasuda T, Saigo K, Urashima T, Toyoda H et al (2006) Comprehensive analysis of microRNA expression patterns in hepatocellular carcinoma and non-tumorous tissues. Oncogene 25:2537–2545CrossRefPubMedGoogle Scholar
  52. 52.
    Tsai WC, Hsu PWC, Lai TC, Chau GY, Lin CW et al (2009) MicroRNA-122, a tumor suppressor MicroRNA that regulates intrahepatic metastasis of hepatocellular carcinoma. Hepatology 49(5):1571–1582CrossRefPubMedGoogle Scholar
  53. 53.
    Yoon SO, Chun SM, Han EH, Choi J, Jang SJ et al (2011) Deregulated expression of microRNA-221 with the potential for prognostic biomarkers in surgically resected hepatocellular carcinoma. Hum Pathol 42(10):1391–1400CrossRefPubMedGoogle Scholar
  54. 54.
    Esquela-Kerscher A, Trang P, Wiggins JF, Patrawala L, Cheng A et al (2008) The let-7 microRNA reduces tumor growth in mouse models of lung cancer. Cell Cycle 7(6):759–764CrossRefPubMedGoogle Scholar
  55. 55.
    Trang P, Medina PP, Wiggins JF, Ruffino L, Kelnar K et al (2010) Regression of murine lung tumors by the let-7 microRNA. Oncogene 29(11):1580–1587CrossRefPubMedGoogle Scholar
  56. 56.
    Seike M, Goto A, Okano T, Bowman ED, Schetter AJ et al (2009) MiR-21 is an EGFR-regulated anti-apoptotic factor in lung cancer in never-smokers. Proc Natl Acad Sci U S A 106(29):12085–12090CrossRefPubMedPubMedCentralGoogle Scholar
  57. 57.
    Yu F, Yao H, Zhu P, Zhang X, Pan Q et al (2007) Let-7 regulates self renewal and tumorigenicity of breast cancer cells. Cell 131(6):1109–1123CrossRefPubMedGoogle Scholar
  58. 58.
    Shimono Y, Zabala M, Cho RW, Lobo N, Dalerba P et al (2009) Downregulation of miRNA-200c links breast cancer stem cells with normal stem cells. Cell 138(3):592–603CrossRefPubMedPubMedCentralGoogle Scholar
  59. 59.
    Si M-L, Zhu S, Wu H, Lu Z, Wu F et al (2007) miR-21-mediated tumor growth. Oncogene 26(19):2799–2803CrossRefPubMedGoogle Scholar
  60. 60.
    Han HB, Gu J, Zuo HJ, Chen ZG, Zhao W et al (2012) Let-7c functions as a metastasis suppressor by targeting MMP11 and PBX3 in colorectal cancer. J Pathol 226(3):544–555CrossRefPubMedGoogle Scholar
  61. 61.
    Akao Y, Nakagawa Y, Naoe T (2006) Let-7 MicroRNA functions as a potential growth suppressor in human colon cancer cells. Biol Pharm Bull 29(5):903–906CrossRefPubMedGoogle Scholar
  62. 62.
    Wang F, Zhang P, Maa Y, Yang J, Moyer MP et al (2012) NIRF is frequently upregulated in colorectal cancer and its oncogenicity can be suppressed by let-7a microRNA. Cancer Lett 314(2):223–231CrossRefPubMedGoogle Scholar
  63. 63.
    Chen Y, Ma C, Zhang W, Chen Z, Ma L (2014) Down regulation of miR-143 is related with tumor size, lymph node metastasis and HPV16 infection in cervical squamous cancer. Diagn Pathol 9:88CrossRefPubMedPubMedCentralGoogle Scholar
  64. 64.
    Link A, Balaguer F, Shen Y, Nagasaka T, Lozano JJ et al (2010) Fecal microRNAs as novel biomarkers for colon cancer screening. Cancer Epidemiol Biomarkers Prev 19(7):1766–1774CrossRefPubMedPubMedCentralGoogle Scholar
  65. 65.
    Medina PP, Nolde M, Slack FJ (2010) OncomiR addiction in an in vivo model of microRNA-21-induced pre-B-cell lymphoma. Nature 467(7311):86–90CrossRefPubMedGoogle Scholar
  66. 66.
    Mavrakis KJ, Wolfe AL, Oricchio E, Palomero T, de Keersmaecker K et al (2010) Genome-wide RNA-mediated interference screen identifies miR-19 targets in notch-induced T-cell acute lymphoblastic leukaemia. Nat Cell Biol 12(4):372–379CrossRefPubMedPubMedCentralGoogle Scholar
  67. 67.
    Chaudhuri AA, So AY-L, Mehta A, Minisandram A, Sinha N et al (2012) Oncomir miR-125b regulates hematopoiesis by targeting the gene Lin28A. Proc Natl Acad Sci U S A 109(11):4233–4238CrossRefPubMedPubMedCentralGoogle Scholar
  68. 68.
    Han J, Li A, Liu H, Wen X, Zhao M et al (2014) Computational identification of microRNAs in the strawberry (Fragaria x Ananassa) genome sequence and validation of their precise sequences by miR-RACE. Gene 536(1):151–162CrossRefPubMedGoogle Scholar
  69. 69.
    Wang M, Tan L, Dijkstra M, van Lom K, Robertus J-L et al (2008) miRNA analysis in B-cell chronic lymphocytic leukaemia: proliferation centres characterized by low miR-150 and high BIC/miR-155 expression. J Pathol 215(1):13–20CrossRefPubMedGoogle Scholar
  70. 70.
    Kalyana-Sundaram S, Kumar-Sinha C, Shankar S, Robinson DR, Wu YM et al (2012) Expressed pseudogenes in the transcriptional landscape of human cancers. Cell 149(7):1622–1634CrossRefPubMedPubMedCentralGoogle Scholar
  71. 71.
    Welch JD, Baran-Gale J, Perou CM, Sethupathy P, Prins JF (2015) Pseudogenes transcribed in breast invasive carcinoma show subtype-specific expression and ceRNA potential. BMC Genomics 16(1):113CrossRefPubMedPubMedCentralGoogle Scholar
  72. 72.
    Han L, Yuan Y, Zheng S, Yang Y, Li J et al (2014) The pan-cancer analysis of pseudogene expression reveals biologically and clinically relevant tumour subtypes. Nat Commun 5:3963PubMedPubMedCentralGoogle Scholar

Copyright information

© Springer Science+Business Media LLC 2018

Authors and Affiliations

  1. 1.Department of Molecular Biology and Genetics, Faculty of Arts and SciencesAhi Evran UniversityKırşehirTurkey
  2. 2.Division of Biochemistry, Department of Basic Sciences, Faculty of PharmacyCumhuriyet UniversitySivasTurkey
  3. 3.Department of Nutrition and Dietetics, Health Sciences FacultyUniversity of Health SciencesIstanbulTurkey

Personalised recommendations