Skip to main content
SpringerLink
Log in

MicroRNAs in Cell Death and Cancer

  • Chapter
  • First Online:
Cell Death Signaling in Cancer Biology and Treatment

Part of the book series: Cell Death in Biology and Diseases ((CELLDEATH))

  • 2298 Accesses

Abstract

MicroRNAs (miRNAs) are small, non-coding RNAs (ncRNAs) that post transcriptionally regulate protein levels by binding to the 3′ UTR of the mRNA. miRNAs are differentially expressed in many solid tumors and often create a unique signature for each tumor type. This chapter explains the function of miRNAs in cancer based on their potential target genes.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 89.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 119.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Holley CL, Topkara VK (2011) An introduction to small non-coding RNAs: miRNA and snoRNA. Cardiovasc Drugs Ther/Sponsored Int Soc Cardiovasc Pharmacother 25(2):151–159

    CAS  Google Scholar 

  2. Mattick JS, Makunin IV (2006) Non-coding RNA. Hum Mol Genet 15(1):R17–R29

    CAS  PubMed  Google Scholar 

  3. Huarte M, Guttman M, Feldser D, Garber M, Koziol MJ, Kenzelmann-Broz D, Khalil AM, Zuk O, Amit I, Rabani M, Attardi LD, Regev A, Lander ES, Jacks T, Rinn JL (2010) A large intergenic noncoding RNA induced by p53 mediates global gene repression in the p53 response. Cell 142(3):409–419

    CAS  PubMed Central  PubMed  Google Scholar 

  4. Carthew RW, Sontheimer EJ (2009) Origins and mechanisms of miRNAs and siRNAs. Cell 136(4):642–655

    CAS  PubMed Central  PubMed  Google Scholar 

  5. Malone CD, Hannon GJ (2009) Small RNAs as guardians of the genome. Cell 136(4):656–668

    CAS  PubMed Central  PubMed  Google Scholar 

  6. Ambros V (2004) The functions of animal microRNAs. Nature 431(7006):350–355

    CAS  PubMed  Google Scholar 

  7. Lee RC, Feinbaum RL, Ambros V (1993) The C. elegans heterochronic gene lin-4 encodes small RNAs with antisense complementarity to lin-14. Cell 75(5):843–854

    CAS  PubMed  Google Scholar 

  8. Wightman B, Ha I, Ruvkun G (1993) Posttranscriptional regulation of the heterochronic gene lin-14 by lin-4 mediates temporal pattern formation in C. elegans. Cell 75(5):855–862

    CAS  PubMed  Google Scholar 

  9. Wiemer EA (2007) The role of microRNAs in cancer: no small matter. Eur J Cancer 43(10):1529–1544

    CAS  PubMed  Google Scholar 

  10. Zhao Y, Samal E, Srivastava D (2005) Serum response factor regulates a muscle-specific microRNA that targets Hand2 during cardiogenesis. Nature 436(7048):214–220

    CAS  PubMed  Google Scholar 

  11. Schaefer A, O’Carroll D, Tan CL, Hillman D, Sugimori M, Llinas R, Greengard P (2007) Cerebellar neurodegeneration in the absence of microRNAs. J Exp Med 204(7):1553–1558

    CAS  PubMed Central  PubMed  Google Scholar 

  12. Taganov KD, Boldin MP, Chang KJ, Baltimore D (2006) NF-kappaB-dependent induction of microRNA miR-146, an inhibitor targeted to signaling proteins of innate immune responses. Proc Nat Acad Sci USA 103(33):12481–12486

    CAS  PubMed Central  PubMed  Google Scholar 

  13. Rodriguez A, Griffiths-Jones S, Ashurst JL, Bradley A (2004) Identification of mammalian microRNA host genes and transcription units. Genome Res 14(10A):1902–1910

    Google Scholar 

  14. Berezikov E, Chung WJ, Willis J, Cuppen E, Lai EC (2007) Mammalian mirtron genes. Mol Cell 28(2):328–336

    CAS  PubMed Central  PubMed  Google Scholar 

  15. Lee Y, Kim M, Han J, Yeom KH, Lee S, Baek SH, Kim VN (2004) MicroRNA genes are transcribed by RNA polymerase II. EMBO J 23(20):4051–4060

    CAS  PubMed Central  PubMed  Google Scholar 

  16. Cai X, Hagedorn CH, Cullen BR (2004) Human microRNAs are processed from capped, polyadenylated transcripts that can also function as mRNAs. RNA 10(12):1957–1966

    CAS  PubMed Central  PubMed  Google Scholar 

  17. Denli AM, Tops BB, Plasterk RH, Ketting RF, Hannon GJ (2004) Processing of primary microRNAs by the microprocessor complex. Nature 432(7014):231–235

    CAS  PubMed  Google Scholar 

  18. Gregory RI, Yan KP, Amuthan G, Chendrimada T, Doratotaj B, Cooch N, Shiekhattar R (2004) The microprocessor complex mediates the genesis of microRNAs. Nature 432(7014):235–240

    CAS  PubMed  Google Scholar 

  19. Senturia R, Faller M, Yin S, Loo JA, Cascio D, Sawaya MR, Hwang D, Clubb RT, Guo F (2010) Structure of the dimerization domain of DiGeorge critical region 8. Protein Sci publ Protein Soc 19(7):1354–1365

    CAS  Google Scholar 

  20. Yi R, Qin Y, Macara IG, Cullen BR (2003) Exportin-5 mediates the nuclear export of pre-microRNAs and short hairpin RNAs. Genes Dev 17(24):3011–3016

    CAS  PubMed Central  PubMed  Google Scholar 

  21. Bussing I, Yang JS, Lai EC, Grosshans H (2010) The nuclear export receptor XPO-1 supports primary miRNA processing in C. elegans and Drosophila. EMBO J 29(11):1830–1839

    PubMed Central  PubMed  Google Scholar 

  22. Gruber JJ, Zatechka DS, Sabin LR, Yong J, Lum JJ, Kong M, Zong WX, Zhang Z, Lau CK, Rawlings J, Cherry S, Ihle JN, Dreyfuss G, Thompson CB (2009) Ars2 links the nuclear cap-binding complex to RNA interference and cell proliferation. Cell 138(2):328–339

    CAS  PubMed Central  PubMed  Google Scholar 

  23. Haase AD, Jaskiewicz L, Zhang H, Laine S, Sack R, Gatignol A, Filipowicz W (2005) TRBP, a regulator of cellular PKR and HIV-1 virus expression, interacts with Dicer and functions in RNA silencing. EMBO Rep 6(10):961–967

    CAS  PubMed Central  PubMed  Google Scholar 

  24. Tsutsumi A, Kawamata T, Izumi N, Seitz H, Tomari Y (2011) Recognition of the pre-miRNA structure by Drosophila dicer-1. Nat Struct Mol Biol 18(10):1153–1158

    CAS  PubMed  Google Scholar 

  25. Saito K, Ishizuka A, Siomi H, Siomi MC (2005) Processing of pre-microRNAs by the dicer-1-loquacious complex in Drosophila cells. PLoS Biol 3(7):e235

    PubMed Central  PubMed  Google Scholar 

  26. Matranga C, Tomari Y, Shin C, Bartel DP, Zamore PD (2005) Passenger-strand cleavage facilitates assembly of siRNA into Ago2-containing RNAi enzyme complexes. Cell 123(4):607–620

    CAS  PubMed  Google Scholar 

  27. Okamura K, Ishizuka A, Siomi H, Siomi MC (2004) Distinct roles for argonaute proteins in small RNA-directed RNA cleavage pathways. Genes Dev 18(14):1655–1666

    CAS  PubMed Central  PubMed  Google Scholar 

  28. Gantier MP, McCoy CE, Rusinova I, Saulep D, Wang D, Xu D, Irving AT, Behlke MA, Hertzog PJ, Mackay F, Williams BR (2011) Analysis of microRNA turnover in mammalian cells following dicer1 ablation. Nucleic Acids Res 39(13):5692–5703

    CAS  PubMed Central  PubMed  Google Scholar 

  29. Krol J, Busskamp V, Markiewicz I, Stadler MB, Ribi S, Richter J, Duebel J, Bicker S, Fehling HJ, Schubeler D, Oertner TG, Schratt G, Bibel M, Roska B, Filipowicz W (2010) Characterizing light-regulated retinal microRNAs reveals rapid turnover as a common property of neuronal microRNAs. Cell 141(4):618–631

    CAS  PubMed  Google Scholar 

  30. Hwang HW, Wentzel EA, Mendell JT (2007) A hexanucleotide element directs microRNA nuclear import. Science 315(5808):97–100

    CAS  PubMed  Google Scholar 

  31. Zhang Z, Zou J, Wang GK, Zhang JT, Huang S, Qin YW, Jing Q (2011) Uracils at nucleotide position 9–11 are required for the rapid turnover of miR-29 family. Nucleic Acids Res 39(10):4387–4395

    CAS  PubMed Central  PubMed  Google Scholar 

  32. Libri V, Helwak A, Miesen P, Santhakumar D, Borger JG, Kudla G, Grey F, Tollervey D, Buck AH (2012) Murine cytomegalovirus encodes a miR-27 inhibitor disguised as a target. Proc Nat Acad Sci USA 109(1):279–284

    CAS  PubMed Central  PubMed  Google Scholar 

  33. Katoh T, Sakaguchi Y, Miyauchi K, Suzuki T, Kashiwabara S, Baba T, Suzuki T (2009) Selective stabilization of mammalian microRNAs by 3’ adenylation mediated by the cytoplasmic poly(A) polymerase GLD-2. Genes Dev 23(4):433–438

    CAS  PubMed Central  PubMed  Google Scholar 

  34. Chatterjee S, Fasler M, Bussing I, Grosshans H (2011) Target-mediated protection of endogenous microRNAs in C. elegans. Dev Cell 20(3):388–396

    CAS  PubMed  Google Scholar 

  35. Hammell CM (2008) The microRNA-argonaute complex: a platform for mRNA modulation. RNA Biol 5(3):123–127

    CAS  PubMed  Google Scholar 

  36. Wang Y, Li Y, Ma Z, Yang W, Ai C (2010) Mechanism of microRNA-target interaction: molecular dynamics simulations and thermodynamics analysis. PLoS Comput Biol 6(7):e1000866

    PubMed Central  PubMed  Google Scholar 

  37. Liu J, Valencia-Sanchez MA, Hannon GJ, Parker R (2005) MicroRNA-dependent localization of targeted mRNAs to mammalian P-bodies. Nat Cell Biol 7(7):719–723

    CAS  PubMed Central  PubMed  Google Scholar 

  38. Bhattacharyya SN, Habermacher R, Martine U, Closs EI, Filipowicz W (2006) Stress-induced reversal of microRNA repression and mRNA P-body localization in human cells. Cold Spring Harb Symp Quant Biol 71:513–521

    CAS  PubMed  Google Scholar 

  39. Ma J, Flemr M, Stein P, Berninger P, Malik R, Zavolan M, Svoboda P, Schultz RM (2010) MicroRNA activity is suppressed in mouse oocytes. Current Biol CB 20(3):265–270

    CAS  Google Scholar 

  40. Suh N, Baehner L, Moltzahn F, Melton C, Shenoy A, Chen J, Blelloch R (2010) MicroRNA function is globally suppressed in mouse oocytes and early embryos. Current Biol CB 20(3):271–277

    CAS  Google Scholar 

  41. Eiring AM, Harb JG, Neviani P, Garton C, Oaks JJ, Spizzo R, Liu S, Schwind S, Santhanam R, Hickey CJ, Becker H, Chandler JC, Andino R, Cortes J, Hokland P, Huettner CS, Bhatia R, Roy DC, Liebhaber SA, Caligiuri MA, Marcucci G, Garzon R, Croce CM, Calin GA, Perrotti D (2010) miR-328 functions as an RNA decoy to modulate hnRNP E2 regulation of mRNA translation in leukemic blasts. Cell 140(5):652–665

    CAS  PubMed Central  PubMed  Google Scholar 

  42. Vasudevan S, Tong Y, Steitz JA (2007) Switching from repression to activation: microRNAs can up-regulate translation. Science 318(5858):1931–1934

    CAS  PubMed  Google Scholar 

  43. Lu J, Getz G, Miska EA, Alvarez-Saavedra E, Lamb J, Peck D, Sweet-Cordero A, Ebert BL, Mak RH, Ferrando AA, Downing JR, Jacks T, Horvitz HR, Golub TR (2005) MicroRNA expression profiles classify human cancers. Nature 435(7043):834–838

    CAS  PubMed  Google Scholar 

  44. Volinia S, Calin GA, Liu CG, Ambs S, Cimmino A, Petrocca F, Visone R, Iorio M, Roldo C, Ferracin M, Prueitt RL, Yanaihara N, Lanza G, Scarpa A, Vecchione A, Negrini M, Harris CC, Croce CM (2006) A microRNA expression signature of human solid tumors defines cancer gene targets. Proc Nat Acad Sci USA 103(7):2257–2261

    CAS  PubMed Central  PubMed  Google Scholar 

  45. Budhu A, Jia HL, Forgues M, Liu CG, Goldstein D, Lam A, Zanetti KA, Ye QH, Qin LX, Croce CM, Tang ZY, Wang XW (2008) Identification of metastasis-related microRNAs in hepatocellular carcinoma. Hepatology 47(3):897–907

    CAS  PubMed  Google Scholar 

  46. Murakami Y, Yasuda T, Saigo K, Urashima T, Toyoda H, Okanoue T, Shimotohno K (2006) Comprehensive analysis of microRNA expression patterns in hepatocellular carcinoma and non-tumorous tissues. Oncogene 25(17):2537–2545

    CAS  PubMed  Google Scholar 

  47. Subramanian S, Lui WO, Lee CH, Espinosa I, Nielsen TO, Heinrich MC, Corless CL, Fire AZ, van de Rijn M (2008) MicroRNA expression signature of human sarcomas. Oncogene 27(14):2015–2026

    CAS  PubMed  Google Scholar 

  48. Navarro A, Gaya A, Martinez A, Urbano-Ispizua A, Pons A, Balague O, Gel B, Abrisqueta P, Lopez-Guillermo A, Artells R, Montserrat E, Monzo M (2008) MicroRNA expression profiling in classic Hodgkin lymphoma. Blood 111(5):2825–2832

    CAS  PubMed  Google Scholar 

  49. Dyrskjot L, Ostenfeld MS, Bramsen JB, Silahtaroglu AN, Lamy P, Ramanathan R, Fristrup N, Jensen JL, Andersen CL, Zieger K, Kauppinen S, Ulhoi BP, Kjems J, Borre M, Orntoft TF (2009) Genomic profiling of microRNAs in bladder cancer: miR-129 is associated with poor outcome and promotes cell death in vitro. Cancer Res 69(11):4851–4860

    CAS  PubMed  Google Scholar 

  50. Calin GA, Ferracin M, Cimmino A, Di Leva G, Shimizu M, Wojcik SE, Iorio MV, Visone R, Sever NI, Fabbri M, Iuliano R, Palumbo T, Pichiorri F, Roldo C, Garzon R, Sevignani C, Rassenti L, Alder H, Volinia S, Liu CG, Kipps TJ, Negrini M, Croce CM (2005) A microRNA signature associated with prognosis and progression in chronic lymphocytic leukemia. N Engl J Med 353(17):1793–1801

    CAS  PubMed  Google Scholar 

  51. Kumar MS, Lu J, Mercer KL, Golub TR, Jacks T (2007) Impaired microRNA processing enhances cellular transformation and tumorigenesis. Nat Genet 39(5):673–677

    CAS  PubMed  Google Scholar 

  52. Calin GA, Dumitru CD, Shimizu M, Bichi R, Zupo S, Noch E, Aldler H, Rattan S, Keating M, Rai K, Rassenti L, Kipps T, Negrini M, Bullrich F, Croce CM (2002) Frequent deletions and down-regulation of micro- RNA genes miR15 and miR16 at 13q14 in chronic lymphocytic leukemia. Proc Nat Acad Sci USA 99(24):15524–15529

    CAS  PubMed Central  PubMed  Google Scholar 

  53. Bonci D, Coppola V, Musumeci M, Addario A, Giuffrida R, Memeo L, D’Urso L, Pagliuca A, Biffoni M, Labbaye C, Bartucci M, Muto G, Peschle C, De Maria R (2008) The miR-15a-miR-16-1 cluster controls prostate cancer by targeting multiple oncogenic activities. Nat Med 14(11):1271–1277

    CAS  PubMed  Google Scholar 

  54. Bottoni A, Piccin D, Tagliati F, Luchin A, Zatelli MC, Degli Uberti EC (2005) miR-15a and miR-16-1 down-regulation in pituitary adenomas. J Cell Physiol 204(1):280–285

    CAS  PubMed  Google Scholar 

  55. Roccaro AM, Sacco A, Thompson B, Leleu X, Azab AK, Azab F, Runnels J, Jia X, Ngo HT, Melhem MR, Lin CP, Ribatti D, Rollins BJ, Witzig TE, Anderson KC, Ghobrial IM (2009) MicroRNAs 15a and 16 regulate tumor proliferation in multiple myeloma. Blood 113(26):6669–6680

    CAS  PubMed Central  PubMed  Google Scholar 

  56. Youle RJ, Strasser A (2008) The BCL-2 protein family: opposing activities that mediate cell death. Nat Rev Mol Cell Biol 9(1):47–59

    CAS  PubMed  Google Scholar 

  57. Cimmino A, Calin GA, Fabbri M, Iorio MV, Ferracin M, Shimizu M, Wojcik SE, Aqeilan RI, Zupo S, Dono M, Rassenti L, Alder H, Volinia S, Liu CG, Kipps TJ, Negrini M, Croce CM (2005) miR-15 and miR-16 induce apoptosis by targeting BCL2. Proc Nat Acad Sci USA 102(39):13944–13949

    CAS  PubMed Central  PubMed  Google Scholar 

  58. Calin GA, Cimmino A, Fabbri M, Ferracin M, Wojcik SE, Shimizu M, Taccioli C, Zanesi N, Garzon R, Aqeilan RI, Alder H, Volinia S, Rassenti L, Liu X, Liu CG, Kipps TJ, Negrini M, Croce CM (2008) MiR-15a and miR-16-1 cluster functions in human leukemia. Proc Nat Acad Sci USA 105(13):5166–5171

    CAS  PubMed Central  PubMed  Google Scholar 

  59. Musumeci M, Coppola V, Addario A, Patrizii M, Maugeri-Sacca M, Memeo L, Colarossi C, Francescangeli F, Biffoni M, Collura D, Giacobbe A, D’Urso L, Falchi M, Venneri MA, Muto G, De Maria R, Bonci D (2011) Control of tumor and microenvironment cross-talk by miR-15a and miR-16 in prostate cancer. Oncogene 30(41):4231–4242

    CAS  PubMed  Google Scholar 

  60. Chen L, Zheng J, Zhang Y, Yang L, Wang J, Ni J, Cui D, Yu C, Cai Z (2011) Tumor-specific expression of microRNA-26a suppresses human hepatocellular carcinoma growth via cyclin-dependent and -independent pathways. Mol Ther J Am Soc Gene Ther 19(8):1521–1528

    CAS  Google Scholar 

  61. Tryndyak VP, Ross SA, Beland FA, Pogribny IP (2009) Down-regulation of the microRNAs miR-34a, miR-127, and miR-200b in rat liver during hepatocarcinogenesis induced by a methyl-deficient diet. Mol Carcinog 48(6):479–487

    CAS  PubMed  Google Scholar 

  62. Tsai WC, Hsu PW, Lai TC, Chau GY, Lin CW, Chen CM, Lin CD, Liao YL, Wang JL, Chau YP, Hsu MT, Hsiao M, Huang HD, Tsou AP (2009) MicroRNA-122, a tumor suppressor microRNA that regulates intrahepatic metastasis of hepatocellular carcinoma. Hepatology 49(5):1571–1582

    CAS  PubMed  Google Scholar 

  63. Mohamed JS, Lopez MA, Boriek AM (2010) Mechanical stretch up-regulates microRNA-26a and induces human airway smooth muscle hypertrophy by suppressing glycogen synthase kinase-3beta. J Biol Chem 285(38):29336–29347

    CAS  PubMed Central  PubMed  Google Scholar 

  64. Harris TE, Albrecht JH, Nakanishi M, Darlington GJ (2001) CCAAT/enhancer-binding protein-alpha cooperates with p21 to inhibit cyclin-dependent kinase-2 activity and induces growth arrest independent of DNA binding. J Biol Chem 276(31):29200–29209

    CAS  PubMed  Google Scholar 

  65. Kota J, Chivukula RR, O’Donnell KA, Wentzel EA, Montgomery CL, Hwang HW, Chang TC, Vivekanandan P, Torbenson M, Clark KR, Mendell JR, Mendell JT (2009) Therapeutic microRNA delivery suppresses tumorigenesis in a murine liver cancer model. Cell 137(6):1005–1017

    CAS  PubMed Central  PubMed  Google Scholar 

  66. Zhu Y, Lu Y, Zhang Q, Liu JJ, Li TJ, Yang JR, Zeng C, Zhuang SM (2011) MicroRNA-26a/b and their host genes cooperate to inhibit the G1/S transition by activating the pRb protein. Nucleic Acids Res 40:4615–4625

    PubMed Central  PubMed  Google Scholar 

  67. Caputo V, Sinibaldi L, Fiorentino A, Parisi C, Catalanotto C, Pasini A, Cogoni C, Pizzuti A (2011) Brain derived neurotrophic factor (BDNF) expression is regulated by microRNAs miR-26a and miR-26b allele-specific binding. PLoS ONE 6(12):e28656

    CAS  PubMed Central  PubMed  Google Scholar 

  68. Lu J, He ML, Wang L, Chen Y, Liu X, Dong Q, Chen YC, Peng Y, Yao KT, Kung HF, Li XP (2011) MiR-26a inhibits cell growth and tumorigenesis of nasopharyngeal carcinoma through repression of EZH2. Cancer Res 71(1):225–233

    CAS  PubMed  Google Scholar 

  69. Hermeking H (2010) The miR-34 family in cancer and apoptosis. Cell Death Differ 17(2):193–199

    CAS  PubMed  Google Scholar 

  70. Liu C, Kelnar K, Liu B, Chen X, Calhoun-Davis T, Li H, Patrawala L, Yan H, Jeter C, Honorio S, Wiggins JF, Bader AG, Fagin R, Brown D, Tang DG (2011) The microRNA miR-34a inhibits prostate cancer stem cells and metastasis by directly repressing CD44. Nat Med 17(2):211–215

    CAS  PubMed Central  PubMed  Google Scholar 

  71. Zeng C, Wang R, Li D, Lin XJ, Wei QK, Yuan Y, Wang Q, Chen W, Zhuang SM (2010) A novel GSK-3 beta-C/EBP alpha-miR-122-insulin-like growth factor 1 receptor regulatory circuitry in human hepatocellular carcinoma. Hepatology 52(5):1702–1712

    CAS  PubMed  Google Scholar 

  72. Xu H, He JH, Xiao ZD, Zhang QQ, Chen YQ, Zhou H, Qu LH (2010) Liver-enriched transcription factors regulate microRNA-122 that targets CUTL1 during liver development. Hepatology 52(4):1431–1442

    CAS  PubMed  Google Scholar 

  73. Gatfield D, Le Martelot G, Vejnar CE, Gerlach D, Schaad O, Fleury-Olela F, Ruskeepaa AL, Oresic M, Esau CC, Zdobnov EM, Schibler U (2009) Integration of microRNA miR-122 in hepatic circadian gene expression. Genes Dev 23(11):1313–1326

    CAS  PubMed Central  PubMed  Google Scholar 

  74. Lanford RE, Hildebrandt-Eriksen ES, Petri A, Persson R, Lindow M, Munk ME, Kauppinen S, Orum H (2010) Therapeutic silencing of microRNA-122 in primates with chronic hepatitis C virus infection. Science 327(5962):198–201

    CAS  PubMed Central  PubMed  Google Scholar 

  75. Esau C, Davis S, Murray SF, Yu XX, Pandey SK, Pear M, Watts L, Booten SL, Graham M, McKay R, Subramaniam A, Propp S, Lollo BA, Freier S, Bennett CF, Bhanot S, Monia BP (2006) miR-122 regulation of lipid metabolism revealed by in vivo antisense targeting. Cell Metab 3(2):87–98

    CAS  PubMed  Google Scholar 

  76. Jopling C (2012) Liver-specific microRNA-122: biogenesis and function. RNA Biol 9(2):137–142

    CAS  PubMed Central  PubMed  Google Scholar 

  77. Bai S, Nasser MW, Wang B, Hsu SH, Datta J, Kutay H, Yadav A, Nuovo G, Kumar P, Ghoshal K (2009) MicroRNA-122 inhibits tumorigenic properties of hepatocellular carcinoma cells and sensitizes these cells to sorafenib. J Biol Chem 284(46):32015–32027

    CAS  PubMed Central  PubMed  Google Scholar 

  78. Fornari F, Gramantieri L, Giovannini C, Veronese A, Ferracin M, Sabbioni S, Calin GA, Grazi GL, Croce CM, Tavolari S, Chieco P, Negrini M, Bolondi L (2009) MiR-122/cyclin G1 interaction modulates p53 activity and affects doxorubicin sensitivity of human hepatocarcinoma cells. Cancer Res 69(14):5761–5767

    CAS  PubMed  Google Scholar 

  79. Akao Y, Nakagawa Y, Hirata I, Iio A, Itoh T, Kojima K, Nakashima R, Kitade Y, Naoe T (2010) Role of anti-oncomirs miR-143 and -145 in human colorectal tumors. Cancer Gene Ther 17(6):398–408

    CAS  PubMed  Google Scholar 

  80. Clape C, Fritz V, Henriquet C, Apparailly F, Fernandez PL, Iborra F, Avances C, Villalba M, Culine S, Fajas L (2009) miR-143 interferes with ERK5 signaling, and abrogates prostate cancer progression in mice. PLoS ONE 4(10):e7542

    PubMed Central  PubMed  Google Scholar 

  81. Wijnhoven BP, Hussey DJ, Watson DI, Tsykin A, Smith CM, Michael MZ, South Australian Oesophageal Research G (2010) MicroRNA profiling of Barrett’s oesophagus and oesophageal adenocarcinoma. Br J Surg 97(6):853–861

    Google Scholar 

  82. Sachdeva M, Mo YY (2010) miR-145-mediated suppression of cell growth, invasion and metastasis. Am J Transl Res 2(2):170–180

    CAS  PubMed Central  PubMed  Google Scholar 

  83. Dou L, Zheng D, Li J, Li Y, Gao L, Wang L, Yu L (2012) Methylation-mediated repression of microRNA-143 enhances MLL-AF4 oncogene expression. Oncogene 31(4):507–517

    CAS  PubMed  Google Scholar 

  84. Xu N, Papagiannakopoulos T, Pan G, Thomson JA, Kosik KS (2009) MicroRNA-145 regulates OCT4, SOX2, and KLF4 and represses pluripotency in human embryonic stem cells. Cell 137(4):647–658

    CAS  PubMed  Google Scholar 

  85. Cho WC, Chow AS, Au JS (2011) MiR-145 inhibits cell proliferation of human lung adenocarcinoma by targeting EGFR and NUDT1. RNA Biol 8(1):125–131

    CAS  PubMed  Google Scholar 

  86. Borralho PM, Simoes AE, Gomes SE, Lima RT, Carvalho T, Ferreira DM, Vasconcelos MH, Castro RE, Rodrigues CM (2011) miR-143 overexpression impairs growth of human colon carcinoma xenografts in mice with induction of apoptosis and inhibition of proliferation. PLoS ONE 6(8):e23787

    CAS  PubMed Central  PubMed  Google Scholar 

  87. Ng EK, Tsang WP, Ng SS, Jin HC, Yu J, Li JJ, Rocken C, Ebert MP, Kwok TT, Sung JJ (2009) MicroRNA-143 targets DNA methyltransferases 3A in colorectal cancer. Br J Cancer 101(4):699–706

    CAS  PubMed Central  PubMed  Google Scholar 

  88. Kent OA, Chivukula RR, Mullendore M, Wentzel EA, Feldmann G, Lee KH, Liu S, Leach SD, Maitra A, Mendell JT (2010) Repression of the miR-143/145 cluster by oncogenic Ras initiates a tumor-promoting feed-forward pathway. Genes Dev 24(24):2754–2759

    CAS  PubMed Central  PubMed  Google Scholar 

  89. Zhang X, Liu S, Hu T, Liu S, He Y, Sun S (2009) Up-regulated microRNA-143 transcribed by nuclear factor kappa B enhances hepatocarcinoma metastasis by repressing fibronectin expression. Hepatology 50(2):490–499

    CAS  PubMed  Google Scholar 

  90. Chan JA, Krichevsky AM, Kosik KS (2005) MicroRNA-21 is an antiapoptotic factor in human glioblastoma cells. Cancer Res 65(14):6029–6033

    CAS  PubMed  Google Scholar 

  91. 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):86–90

    CAS  PubMed  Google Scholar 

  92. Davis BN, Hilyard AC, Lagna G, Hata A (2008) SMAD proteins control DROSHA-mediated microRNA maturation. Nature 454(7200):56–61

    CAS  PubMed Central  PubMed  Google Scholar 

  93. Polytarchou C, Iliopoulos D, Hatziapostolou M, Kottakis F, Maroulakou I, Struhl K, Tsichlis PN (2011) Akt2 regulates all Akt isoforms and promotes resistance to hypoxia through induction of miR-21 upon oxygen deprivation. Cancer Res 71(13):4720–4731

    CAS  PubMed Central  PubMed  Google Scholar 

  94. Du J, Yang S, An D, Hu F, Yuan W, Zhai C, Zhu T (2009) BMP-6 inhibits microRNA-21 expression in breast cancer through repressing deltaEF1 and AP-1. Cell Res 19(4):487–496

    CAS  PubMed  Google Scholar 

  95. Yang CH, Yue J, Fan M, Pfeffer LM (2010) IFN induces miR-21 through a signal transducer and activator of transcription 3-dependent pathway as a suppressive negative feedback on IFN-induced apoptosis. Cancer Res 70(20):8108–8116

    CAS  PubMed Central  PubMed  Google Scholar 

  96. Seike M, Goto A, Okano T, Bowman ED, Schetter AJ, Horikawa I, Mathe EA, Jen J, Yang P, Sugimura H, Gemma A, Kudoh S, Croce CM, Harris CC (2009) MiR-21 is an EGFR-regulated anti-apoptotic factor in lung cancer in never-smokers. Proc Nat Acad Sci USA 106(29):12085–12090

    CAS  PubMed Central  PubMed  Google Scholar 

  97. Bakirtzi K, Hatziapostolou M, Karagiannides I, Polytarchou C, Jaeger S, Iliopoulos D, Pothoulakis C (2011) Neurotensin signaling activates microRNAs-21 and -155 and Akt, promotes tumor growth in mice, and is increased in human colon tumors. Gastroenterology 141(5):1749–1761, e1741

    Google Scholar 

  98. Wang K, Li PF (2010) Foxo3a regulates apoptosis by negatively targeting miR-21. J Biol Chem 285(22):16958–16966

    CAS  PubMed Central  PubMed  Google Scholar 

  99. Fujita S, Ito T, Mizutani T, Minoguchi S, Yamamichi N, Sakurai K, Iba H (2008) miR-21 gene expression triggered by AP-1 is sustained through a double-negative feedback mechanism. J Mol Biol 378(3):492–504

    CAS  PubMed  Google Scholar 

  100. Krichevsky AM, Gabriely G (2009) miR-21: a small multi-faceted RNA. J Cell Mol Med 13(1):39–53

    CAS  PubMed  Google Scholar 

  101. Zhu S, Wu H, Wu F, Nie D, Sheng S, Mo YY (2008) MicroRNA-21 targets tumor suppressor genes in invasion and metastasis. Cell Res 18(3):350–359

    CAS  PubMed  Google Scholar 

  102. Garofalo M, Di Leva G, Romano G, Nuovo G, Suh SS, Ngankeu A, Taccioli C, Pichiorri F, Alder H, Secchiero P, Gasparini P, Gonelli A, Costinean S, Acunzo M, Condorelli G, Croce CM (2009) miR-221&222 regulate TRAIL resistance and enhance tumorigenicity through PTEN and TIMP3 downregulation. Cancer Cell 16(6):498–509

    CAS  PubMed Central  PubMed  Google Scholar 

  103. Shah MY, Calin GA (2011) MicroRNAs miR-221 and miR-222: a new level of regulation in aggressive breast cancer. Genome Med 3(8):56

    PubMed Central  PubMed  Google Scholar 

  104. Fornari F, Gramantieri L, Ferracin M, Veronese A, Sabbioni S, Calin GA, Grazi GL, Giovannini C, Croce CM, Bolondi L, Negrini M (2008) MiR-221 controls CDKN1C/p57 and CDKN1B/p27 expression in human hepatocellular carcinoma. Oncogene 27(43):5651–5661

    CAS  PubMed  Google Scholar 

  105. Garofalo M, Romano G, Di Leva G, Nuovo G, Jeon YJ, Ngankeu A, Sun J, Lovat F, Alder H, Condorelli G, Engelman JA, Ono M, Rho JK, Cascione L, Volinia S, Nephew KP, Croce CM (2011) EGFR and MET receptor tyrosine kinase-altered microRNA expression induces tumorigenesis and gefitinib resistance in lung cancers. Nat Med 18(1):74–82

    PubMed Central  PubMed  Google Scholar 

  106. Galardi S, Mercatelli N, Farace MG, Ciafre SA (2011) NF-kB and c-Jun induce the expression of the oncogenic miR-221 and miR-222 in prostate carcinoma and glioblastoma cells. Nucleic Acids Res 39(9):3892–3902

    CAS  PubMed Central  PubMed  Google Scholar 

  107. Stinson S, Lackner MR, Adai AT, Yu N, Kim HJ, O’Brien C, Spoerke J, Jhunjhunwala S, Boyd Z, Januario T, Newman RJ, Yue P, Bourgon R, Modrusan Z, Stern HM, Warming S, de Sauvage FJ, Amler L, Yeh RF, Dornan D (2011) TRPS1 targeting by miR-221/222 promotes the epithelial-to-mesenchymal transition in breast cancer. Sci Signal 4(177):ra41

    PubMed  Google Scholar 

  108. Di Leva G, Gasparini P, Piovan C, Ngankeu A, Garofalo M, Taccioli C, Iorio MV, Li M, Volinia S, Alder H, Nakamura T, Nuovo G, Liu Y, Nephew KP, Croce CM (2010) MicroRNA cluster 221–222 and estrogen receptor alpha interactions in breast cancer. J Natl Cancer Inst 102(10):706–721

    PubMed Central  PubMed  Google Scholar 

  109. le Sage C, Nagel R, Egan DA, Schrier M, Mesman E, Mangiola A, Anile C, Maira G, Mercatelli N, Ciafre SA, Farace MG, Agami R (2007) Regulation of the p27(Kip1) tumor suppressor by miR-221 and miR-222 promotes cancer cell proliferation. EMBO J 26(15):3699–3708

    PubMed Central  PubMed  Google Scholar 

  110. Zhang CZ, Zhang JX, Zhang AL, Shi ZD, Han L, Jia ZF, Yang WD, Wang GX, Jiang T, You YP, Pu PY, Cheng JQ, Kang CS (2010) MiR-221 and miR-222 target PUMA to induce cell survival in glioblastoma. Mol Cancer 9:229

    PubMed Central  PubMed  Google Scholar 

  111. Lu Y, Roy S, Nuovo G, Ramaswamy B, Miller T, Shapiro C, Jacob ST, Majumder S (2011) Anti-microRNA-222 (anti-miR-222) and -181B suppress growth of tamoxifen-resistant xenografts in mouse by targeting TIMP3 protein and modulating mitogenic signal. J Biol Chem 286(49):42292–42302

    CAS  PubMed Central  PubMed  Google Scholar 

  112. Olive V, Jiang I, He L (2010) mir-17-92, a cluster of miRNAs in the midst of the cancer network. Int J Biochem Cell Biol 42(8):1348–1354

    CAS  PubMed Central  PubMed  Google Scholar 

  113. Mu P, Han YC, Betel D, Yao E, Squatrito M, Ogrodowski P, de Stanchina E, D’Andrea A, Sander C, Ventura A (2009) Genetic dissection of the miR-17~92 cluster of microRNAs in Myc-induced B-cell lymphomas. Genes Dev 23(24):2806–2811

    CAS  PubMed Central  PubMed  Google Scholar 

  114. De Brouwer S, Mestdagh P, Lambertz I, Pattyn F, De Paepe A, Westermann F, Schroeder C, Schulte JH, Schramm A, De Preter K, Vandesompele J, Speleman F (2011) Dickkopf-3 is regulated by the MYCN-induced miR-17-92 cluster in neuroblastoma. Int J Cancer J Int Du Cancer 130(11):2591–2598

    Google Scholar 

  115. Yan HL, Xue G, Mei Q, Wang YZ, Ding FX, Liu MF, Lu MH, Tang Y, Yu HY, Sun SH (2009) Repression of the miR-17-92 cluster by p53 has an important function in hypoxia-induced apoptosis. EMBO J 28(18):2719–2732

    CAS  PubMed Central  PubMed  Google Scholar 

  116. Dews M, Fox JL, Hultine S, Sundaram P, Wang W, Liu YY, Furth E, Enders GH, El-Deiry W, Schelter JM, Cleary MA, Thomas-Tikhonenko A (2010) The myc-miR-17~92 axis blunts TGF{beta} signaling and production of multiple TGF{beta}-dependent antiangiogenic factors. Cancer Res 70(20):8233–8246

    CAS  PubMed Central  PubMed  Google Scholar 

  117. Hong L, Lai M, Chen M, Xie C, Liao R, Kang YJ, Xiao C, Hu WY, Han J, Sun P (2010) The miR-17-92 cluster of microRNAs confers tumorigenicity by inhibiting oncogene-induced senescence. Cancer Res 70(21):8547–8557

    CAS  PubMed Central  PubMed  Google Scholar 

  118. Kim K, Chadalapaka G, Lee SO, Yamada D, Sastre-Garau X, Defossez PA, Park YY, Lee JS, Safe S (2012) Identification of oncogenic microRNA-17-92/ZBTB4/specificity protein axis in breast cancer. Oncogene 31(8):1034–1044

    CAS  PubMed Central  PubMed  Google Scholar 

  119. van Haaften G, Agami R (2010) Tumorigenicity of the miR-17-92 cluster distilled. Genes Dev 24(1):1–4

    PubMed Central  PubMed  Google Scholar 

  120. Petrocca F, Vecchione A, Croce CM (2008) Emerging role of miR-106b-25/miR-17-92 clusters in the control of transforming growth factor beta signaling. Cancer Res 68(20):8191–8194

    CAS  PubMed  Google Scholar 

  121. Li Y, Tan W, Neo TW, Aung MO, Wasser S, Lim SG, Tan TM (2009) Role of the miR-106b-25 microRNA cluster in hepatocellular carcinoma. Cancer Sci 100(7):1234–1242

    CAS  PubMed  Google Scholar 

  122. Bueno MJ, Gomez de Cedron M, Laresgoiti U, Fernandez-Piqueras J, Malumbres M (2010) Multiple E2F-induced microRNAs prevent replicative stress in response to mitogenic signaling. Mol Cell Biol 30(12):2983–2995

    CAS  PubMed Central  PubMed  Google Scholar 

  123. Kan T, Sato F, Ito T, Matsumura N, David S, Cheng Y, Agarwal R, Paun BC, Jin Z, Olaru AV, Selaru FM, Hamilton JP, Yang J, Abraham JM, Mori Y, Meltzer SJ (2009) The miR-106b-25 polycistron, activated by genomic amplification, functions as an oncogene by suppressing p21 and Bim. Gastroenterology 136(5):1689–1700

    CAS  PubMed Central  PubMed  Google Scholar 

  124. Fang L, Deng Z, Shatseva T, Yang J, Peng C, Du WW, Yee AJ, Ang LC, He C, Shan SW, Yang BB (2011) MicroRNA miR-93 promotes tumor growth and angiogenesis by targeting integrin-beta8. Oncogene 30(7):806–821

    CAS  PubMed  Google Scholar 

  125. Poliseno L, Salmena L, Riccardi L, Fornari A, Song MS, Hobbs RM, Sportoletti P, Varmeh S, Egia A, Fedele G, Rameh L, Loda M, Pandolfi PP (2010) Identification of the miR-106b~25 microRNA cluster as a proto-oncogenic PTEN-targeting intron that cooperates with its host gene MCM7 in transformation. Sci Signal 3(117):ra29

    PubMed Central  PubMed  Google Scholar 

  126. Lu Z, Li Y, Takwi A, Li B, Zhang J, Conklin DJ, Young KH, Martin R, Li Y (2011) miR-301a as an NF-kappaB activator in pancreatic cancer cells. EMBO J 30(1):57–67

    CAS  PubMed Central  PubMed  Google Scholar 

  127. Chen Y, Gorski DH (2008) Regulation of angiogenesis through a microRNA (miR-130a) that down-regulates antiangiogenic homeobox genes GAX and HOXA5. Blood 111(3):1217–1226

    CAS  PubMed Central  PubMed  Google Scholar 

  128. Yeung ML, Yasunaga J, Bennasser Y, Dusetti N, Harris D, Ahmad N, Matsuoka M, Jeang KT (2008) Roles for microRNAs, miR-93 and miR-130b, and tumor protein 53-induced nuclear protein 1 tumor suppressor in cell growth dysregulation by human T-cell lymphotrophic virus 1. Cancer Res 68(21):8976–8985

    CAS  PubMed Central  PubMed  Google Scholar 

  129. Lai KW, Koh KX, Loh M, Tada K, Subramaniam MM, Lim XY, Vaithilingam A, Salto-Tellez M, Iacopetta B, Ito Y, Soong R, Singapore Gastric Cancer C (2010) MicroRNA-130b regulates the tumour suppressor RUNX3 in gastric cancer. Eur J Cancer 46(8):1456–1463

    Google Scholar 

  130. Borgdorff V, Lleonart ME, Bishop CL, Fessart D, Bergin AH, Overhoff MG, Beach DH (2010) Multiple microRNAs rescue from Ras-induced senescence by inhibiting p21(Waf1/Cip1). Oncogene 29(15):2262–2271

    CAS  PubMed  Google Scholar 

  131. Shi W, Gerster K, Alajez NM, Tsang J, Waldron L, Pintilie M, Hui AB, Sykes J, P’ng C, Miller N, McCready D, Fyles A, Liu FF (2011) MicroRNA-301 mediates proliferation and invasion in human breast cancer. Cancer Res 71(8):2926–2937

    CAS  PubMed  Google Scholar 

  132. Kluiver J, Poppema S, de Jong D, Blokzijl T, Harms G, Jacobs S, Kroesen BJ, van den Berg A (2005) BIC and miR-155 are highly expressed in Hodgkin, primary mediastinal and diffuse large B cell lymphomas. J Pathol 207(2):243–249

    CAS  PubMed  Google Scholar 

  133. Costinean S, Zanesi N, Pekarsky Y, Tili E, Volinia S, Heerema N, Croce CM (2006) Pre-B cell proliferation and lymphoblastic leukemia/high-grade lymphoma in E(mu)-miR155 transgenic mice. Proc Nat Acad Sci USA 103(18):7024–7029

    CAS  PubMed Central  PubMed  Google Scholar 

  134. Faraoni I, Antonetti FR, Cardone J, Bonmassar E (2009) miR-155 gene: a typical multifunctional microRNA. Biochim Biophys Acta 1792(6):497–505

    CAS  PubMed  Google Scholar 

  135. Gironella M, Seux M, Xie MJ, Cano C, Tomasini R, Gommeaux J, Garcia S, Nowak J, Yeung ML, Jeang KT, Chaix A, Fazli L, Motoo Y, Wang Q, Rocchi P, Russo A, Gleave M, Dagorn JC, Iovanna JL, Carrier A, Pebusque MJ, Dusetti NJ (2007) Tumor protein 53-induced nuclear protein 1 expression is repressed by miR-155, and its restoration inhibits pancreatic tumor development. Proc Nat Acad Sci USA 104(41):16170–16175

    CAS  PubMed Central  PubMed  Google Scholar 

  136. Kong W, He L, Coppola M, Guo J, Esposito NN, Coppola D, Cheng JQ (2010) MicroRNA-155 regulates cell survival, growth, and chemosensitivity by targeting FOXO3a in breast cancer. J Biol Chem 285(23):17869–17879

    CAS  PubMed Central  PubMed  Google Scholar 

  137. Lee DW, Futami M, Carroll M, Feng Y, Wang Z, Fernandez M, Whichard Z, Chen Y, Kornblau S, Shpall EJ, Bueso-Ramos CE, Corey SJ (2012) Loss of SHIP-1 protein expression in high-risk myelodysplastic syndromes is associated with miR-210 and miR-155. Oncogene 31(37):4085–4094

    CAS  PubMed  Google Scholar 

  138. Dagan LN, Jiang X, Bhatt S, Cubedo E, Rajewsky K, Lossos IS (2012) miR-155 regulates HGAL expression and increases lymphoma cell motility. Blood 119(2):513–520

    CAS  PubMed Central  PubMed  Google Scholar 

  139. Jiang S, Zhang HW, Lu MH, He XH, Li Y, Gu H, Liu MF, Wang ED (2010) MicroRNA-155 functions as an OncomiR in breast cancer by targeting the suppressor of cytokine signaling 1 gene. Cancer Res 70(8):3119–3127

    CAS  PubMed  Google Scholar 

  140. Vargova K, Curik N, Burda P, Basova P, Kulvait V, Pospisil V, Savvulidi F, Kokavec J, Necas E, Berkova A, Obrtlikova P, Karban J, Mraz M, Pospisilova S, Mayer J, Trneny M, Zavadil J, Stopka T (2011) MYB transcriptionally regulates the miR-155 host gene in chronic lymphocytic leukemia. Blood 117(14):3816–3825

    CAS  PubMed  Google Scholar 

  141. Wang B, Majumder S, Nuovo G, Kutay H, Volinia S, Patel T, Schmittgen TD, Croce C, Ghoshal K, Jacob ST (2009) Role of microRNA-155 at early stages of hepatocarcinogenesis induced by choline-deficient and amino acid-defined diet in C57BL/6 mice. Hepatology 50(4):1152–1161

    CAS  PubMed Central  PubMed  Google Scholar 

  142. Chang S, Wang RH, Akagi K, Kim KA, Martin BK, Cavallone L, Kathleen Cuningham Foundation Consortium for Research into Familial Breast C, Haines DC, Basik M, Mai P, Poggi E, Isaacs C, Looi LM, Mun KS, Greene MH, Byers SW, Teo SH, Deng CX, Sharan SK (2011) Tumor suppressor BRCA1 epigenetically controls oncogenic microRNA-155. Nat Med 17(10):1275–1282

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Division of Pharmaceutics, College of Pharmacy, Ohio State University, Columbus, OH, USA

    Jong Kook Park & Thomas D. Schmittgen

Authors
  1. Jong Kook Park
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Thomas D. Schmittgen
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Thomas D. Schmittgen .

Editor information

Editors and Affiliations

  1. Department of Medicine, University of Pittsburgh Division of Hematology/Oncology, Pittsburgh, Pennsylvania, USA

    Daniel E. Johnson

Rights and permissions

Reprints and permissions

Copyright information

© 2013 Springer Science+Business Media New York

About this chapter

Cite this chapter

Park, J.K., Schmittgen, T.D. (2013). MicroRNAs in Cell Death and Cancer. In: Johnson, D. (eds) Cell Death Signaling in Cancer Biology and Treatment. Cell Death in Biology and Diseases. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4614-5847-0_5

Download citation

Publish with us

Policies and ethics

Search

Navigation