Skip to main content

Function of miRNAs in Tumor Cell Proliferation

  • Chapter
  • First Online:
MicroRNA in Cancer

Abstract

MicroRNAs (miR) are a class of multifunctional, small, non-coding, singled-stranded molecules that regulate the stability or translational efficiency of targeted messenger RNAs. According to the miRBase Sequence Database (http://www.mirbase.org/index.shtml), more than 1,000 miR sequences have been identified from the tissues or cells of human origin. miRNAs are transcribed from the genome mostly by RNA polymerase II into primary miRNAs (called pri-miRNA) which are usually around 1 kb in length. pri-miRNAs are further processed in the nucleus by a ribonucleases complex composed of Drosha and DGCR8 into precursor miRNAs (called pre-miRNAs) which are around 70–90 nucleotides in length with imperfectly complementary stem-loop-stem structures. The pre-miRNA is then transported by exportin-5, a pre-miRNA-specific export carrier, to the cytoplasm where the pre-miRNA is cleaved by another ribonuclease, Dicer, into a double-stranded miRNA which consists of a mature miRNA sequence of about 17–25 nucleotides long and a miRNA* fragment (derived from the opposite strand to the mature miRNA strand). The mature miRNA is assembled into a ribonucleoprotein complex known as RNA-induced silencing complex (RISC) that includes Argonaute protein [1]. The miR-RISC complex could lead to base-pairing interactions between a miRNA and the binding site of its target mRNAs within the 3′ untranslated region (3′UTR). The interaction could lead to endonucleotic cleavage of the target mRNA or interference with its ability to be translated depending on the base-pairing complementarity between the miRNA and the target mRNA [2, 3].

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

Access this chapter

eBook
USD 16.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 109.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 109.99
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. Meister G, Landthaler M, Patkaniowska A, Dorsett Y, Teng G, Tuschl T (2004) Human Argonaute2 mediates RNA cleavage targeted by miRNAs and siRNAs. Mol Cell 15:185–197

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  3. Cullen BR (2004) Transcription and processing of human microRNA precursors. Mol Cell 16:861–865

    Article  PubMed  CAS  Google Scholar 

  4. Krek A, Grun D, Poy MN, Wolf R, Rosenberg L, Epstein EJ, MacMenamin P, da Piedade I, Gunsalus KC, Stoffel M, Rajewsky N (2005) Combinatorial microRNA target predictions. Nat Genet 37:495–500

    Article  PubMed  CAS  Google Scholar 

  5. Cui Q, Yu Z, Purisima EO, Wang E (2006) Principles of microRNA regulation of a human cellular signaling network. Mol Syst Biol 2:46

    Article  PubMed  Google Scholar 

  6. Tili E, Michaille JJ, Gandhi V, Plunkett W, Sampath D, Calin GA (2007) MiRNAs and their potential for use against cancer and other diseases. Future Oncol 3:521–537

    Article  PubMed  CAS  Google Scholar 

  7. Calin GA, Croce CM (2006) MicroRNA signatures in human cancers. Nat Rev Cancer 6:857–866

    Article  PubMed  CAS  Google Scholar 

  8. Calin GA, Sevignani C, Dumitru CD, Hyslop T, Noch E, Yendamuri S, Shimizu M, Rattan S, Bullrich F, Negrini M, Croce CM (2004) Human microRNA genes are frequently located at fragile sites and genomic regions involved in cancers. Proc Natl Acad Sci USA 101:2999–3004

    Article  PubMed  CAS  Google Scholar 

  9. Zhang B, Pan X, Cobb GP, Anderson TA (2007) MicroRNAs as oncogenes and tumor suppressors. Dev Biol 302:1–12

    Article  PubMed  CAS  Google Scholar 

  10. Esquela-Kerscher A, Slack FJ. (2006) Oncomirs—microRNAs with a role in cancer. Nat Rev Cancer 6:259–269

    Article  PubMed  CAS  Google Scholar 

  11. Cummins JM, Velculescu VE (2006) Implications of micro-RNA profiling for cancer diagnosis. Oncogene 25:6220–6227

    Article  PubMed  CAS  Google Scholar 

  12. Takamizawa J, Konishi H, Yanagisawa K, Tomida S, Osada H, Endoh H, Harano T, Yatabe Y, Nagino M, Nimura Y, Mitsudomi T, Takahashi T (2004) Reduced expression of the let-7 microRNAs in human lung cancers in association with shortened postoperative survival. Cancer Res 64:3753–3756

    Article  PubMed  CAS  Google Scholar 

  13. 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 Natl Acad Sci USA 99:15524–15529

    Article  PubMed  CAS  Google Scholar 

  14. Yu Z, Wang C, Wang M, Li Z, Casimiro MC, Liu M, Wu K, Whittle J, Ju X, Hyslop T, McCue P, Pestell RG (2008) A cyclin D1/microRNA 17/20 regulatory feedback loop in control of breast cancer cell proliferation. J Cell Biol 182:509–517

    Article  PubMed  CAS  Google Scholar 

  15. Iorio MV, Ferracin M, Liu CG, Veronese A, Spizzo R, Sabbioni S, Magri E, Pedriali M, Fabbri M, Campiglio M, Menard S, Palazzo JP, Rosenberg A, Musiani P, Volinia S, Nenci I, Calin GA, Querzoli P, Negrini M, Croce CM (2005) MicroRNA gene expression deregulation in human breast cancer. Cancer Res 65:7065–7070

    Article  PubMed  CAS  Google Scholar 

  16. Jiang J, Lee EJ, Gusev Y, Schmittgen TD (2005) Real-time expression profiling of microRNA precursors in human cancer cell lines. Nucleic Acids Res 33:5394–5403

    Article  PubMed  CAS  Google Scholar 

  17. Zhang L, Huang J, Yang N, Greshock J, Megraw MS, Giannakakis A, Liang S, Naylor TL, Barchetti A, Ward MR, Yao G, Medina A, O’Brien-Jenkins A, Katsaros D, Hatzigeorgiou A, Gimotty PA, Weber BL, Coukos G (2006) microRNAs exhibit high frequency genomic alterations in human cancer. Proc Natl Acad Sci USA 103:9136–9141

    Article  PubMed  CAS  Google Scholar 

  18. 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 25:2537–2545

    Article  PubMed  CAS  Google Scholar 

  19. Yanaihara N, Caplen N, Bowman E, Seike M, Kumamoto K, Yi M, Stephens RM, Okamoto A, Yokota J, Tanaka T, Calin GA, Liu CG, Croce CM, Harris CC (2006) Unique microRNA molecular profiles in lung cancer diagnosis and prognosis. Cancer Cell 9:189–198

    Article  PubMed  CAS  Google Scholar 

  20. Porkka KP, Pfeiffer MJ, Waltering KK, Vessella RL, Tammela TL, Visakorpi T (2007) MicroRNA expression profiling in prostate cancer. Cancer Res 67:6130–6135

    Article  PubMed  CAS  Google Scholar 

  21. Gottardo F, Liu CG, Ferracin M, Calin GA, Fassan M, Bassi P, Sevignani C, Byrne D, Negrini M, Pagano F, Gomella LG, Croce CM, Baffa R (2007) Micro-RNA profiling in kidney and bladder cancers. Urol Oncol 25:387–392

    Article  PubMed  CAS  Google Scholar 

  22. Schepeler T, Reinert JT, Ostenfeld MS, Christensen LL, Silahtaroglu AN, Dyrskjot L, Wiuf C, Sorensen FJ, Kruhoffer M, Laurberg S, Kauppinen S, Orntoft TF, Andersen CL (2008) Diagnostic and prognostic microRNAs in stage II colon cancer. Cancer Res 68:6416–6424

    Article  PubMed  CAS  Google Scholar 

  23. Pestell RG, Albanese C, Reutens AT, Segall JE, Lee RJ, Arnold A (1999) The cyclins and cyclin-dependent kinase inhibitors in harmonal regulation of prolifertion and differentiation. Endocr Rev Aug 20(4):501–534

    Article  CAS  Google Scholar 

  24. Fu M, Wang C, Li Z, Sakamaki T, Pestell RG (2004) Minireview: Cyclin D1: Normal and abnormal functions. Endocrinology 145:5439–5447

    Article  PubMed  CAS  Google Scholar 

  25. Jiang W, Kahn SM, Tomita N, Zhang YJ, Lu SH, Weinstein IB (1992) Amplification and expression of the human cyclin D gene in esophageal cancer. Cancer Res 52:2980–2983

    PubMed  CAS  Google Scholar 

  26. Lazzereschi D, Sambuco L, Carnovale Scalzo C, Ranieri A, Mincione G, Nardi F, Colletta G (1998) Cyclin D1 and Cyclin E expression in malignant thyroid cells and in human thyroid carcinomas. Int J Cancer 76:806–811

    Article  PubMed  CAS  Google Scholar 

  27. O’Donnell KA, Wentzel EA, Zeller KI, Dang CV, Mendell JT (2005) C-Myc-regulated microRNAs modulate E2F1 expression. Nature 435:839–843

    Article  PubMed  Google Scholar 

  28. Lee RJ, Albanese C, Fu M, D’Amico M, Lin B, Watanabe G, Haines GK 3rd, Siegel PM, Hung MC, Yarden Y, Horowitz JM, Muller WJ, Pestell RG (2000) Cyclin D1 is required for transformation by activated Neu and is induced through an E2F-dependent signaling pathway. Mol Cell Biol Jan 20(2):672–683

    CAS  Google Scholar 

  29. Lu Y, Thomson JM, Wong HY, Hammond SM, Hogan BL (2007) Transgenic over-expression of the microRNA miR-17-92 cluster promotes proliferation and inhibits differentiation of lung epithelial progenitor cells. Dev Biol 310:442–453

    Article  PubMed  CAS  Google Scholar 

  30. Miller TE, Ghoshal K, Ramaswamy B, Roy S, Datta J, Shapiro CL, Jacob S, Majumder S (2008) MicroRNA-221/222 confers tamoxifen resistance in breast cancer by targeting p27Kip1. J Biol Chem 283:29897–29903

    Article  PubMed  CAS  Google Scholar 

  31. 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 14:1271–1277

    Article  PubMed  CAS  Google Scholar 

  32. 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 204:280–285

    Article  PubMed  CAS  Google Scholar 

  33. Deshpande A, Pastore A, Deshpande AJ, Zimmermann Y, Hutter G, Weinkauf M, Buske C, Hiddemann W, Dreyling M (2009) 3’UTR mediated regulation of the cyclin D1 proto-oncogene. Cell Cycle 8:3584–3592

    Article  PubMed  Google Scholar 

  34. Liu Q, Fu H, Sun F, Zhang H, Tie Y, Zhu J, Xing R, Sun Z, Zheng X (2008) MiR-16 family induces cell cycle arrest by regulating multiple cell cycle genes. Nucleic Acids Res 36:5391–5404

    Article  PubMed  CAS  Google Scholar 

  35. Yu Z, Baserga R, Chen L, Wang C, Lisanti MP, Pestell RG (2010) MicroRNA, cell cycle, and human breast cancer. Am J Pathol 176:1058–1064

    Article  PubMed  CAS  Google Scholar 

  36. Kim YK, Yu J, Han TS, Park SY, Namkoong B, Kim DH, Hur K, Yoo MW, Lee HJ, Yang HK, Kim VN (2009) Functional links between clustered microRNAs: suppression of cell-cycle inhibitors by microRNA clusters in gastric cancer. Nucleic Acids Res 37:1672–1681

    Article  PubMed  CAS  Google Scholar 

  37. Schetter AJ, Leung SY, Sohn JJ, Zanetti KA, Bowman ED, Yanaihara N, Yuen ST, Chan TL, Kwong DL, Au GK, Liu CG, Calin GA, Croce CM, Harris CC (2008) MicroRNA expression profiles associated with prognosis and therapeutic outcome in colon adenocarcinoma. JAMA 299:425–436

    Article  PubMed  CAS  Google Scholar 

  38. Yang N, Kaur S, Volinia S, Greshock J, Lassus H, Hasegawa K, Liang S, Leminen A, Deng S, Smith L, Johnstone CN, Chen XM, Liu CG, Huang Q, Katsaros D, Calin GA, Weber BL, Butzow R, Croce CM, Coukos G, Zhang L (2008) MicroRNA microarray identifies Let-7i as a novel biomarker and therapeutic target in human epithelial ovarian cancer. Cancer Res 68:10307–10314

    Article  PubMed  CAS  Google Scholar 

  39. Yu F, Yao H, Zhu P, Zhang X, Pan Q, Gong C, Huang Y, Hu X, Su F, Lieberman J, Song E (2007) let-7 regulates self renewal and tumorigenicity of breast cancer cells. Cell 131:1109–1123

    Article  PubMed  CAS  Google Scholar 

  40. Mayr C, Hemann MT, Bartel DP. (2007) Disrupting the pairing between let-7 and Hmga2 enhances oncogenic transformation. Science 315:1576–1579

    Article  PubMed  CAS  Google Scholar 

  41. Johnson SM, Grosshans H, Shingara J, Byrom M, Jarvis R, Cheng A, Labourier E, Reinert KL, Brown D, Slack FJ (2005) RAS is regulated by the let-7 microRNA family. Cell 120:635–647

    Article  PubMed  CAS  Google Scholar 

  42. Tsang WP, Kwok TT (2008) Let-7a microRNA suppresses therapeutics-induced cancer cell death by targeting caspase-3. Apoptosis 13:1215–1222

    Article  PubMed  CAS  Google Scholar 

  43. Sampson VB, Rong NH, Han J, Yang Q, Aris V, Soteropoulos P, Petrelli NJ, Dunn SP, Krueger LJ (2007) MicroRNA let-7a down-regulates MYC and reverts MYC-induced growth in Burkitt lymphoma cells. Cancer Res 67:9762–9770

    Article  PubMed  CAS  Google Scholar 

  44. Schultz J, Lorenz P, Gross G, Ibrahim S, Kunz M (2008) MicroRNA let-7b targets important cell cycle molecules in malignant melanoma cells and interferes with anchorage-independent growth. Cell Res 18:549–557

    Article  PubMed  CAS  Google Scholar 

  45. Johnson CD, Esquela-Kerscher A, Stefani G, Byrom M, Kelnar K, Ovcharenko D, Wilson M, Wang X, Shelton J, Shingara J, Chin L, Brown D, Slack FJ (2007) The let-7 microRNA represses cell proliferation pathways in human cells. Cancer Res 67:7713–7722

    Article  PubMed  CAS  Google Scholar 

  46. Garzon R, Heaphy CE, Havelange V, Fabbri M, Volinia S, Tsao T, Zanesi N, Kornblau SM, Marcucci G, Calin GA, Andreeff M, Croce CM (2009) MicroRNA 29b functions in acute myeloid leukemia. Blood 114:5331–5341

    Article  PubMed  CAS  Google Scholar 

  47. Wang H, Garzon R, Sun H, Ladner KJ, Singh R, Dahlman J, Cheng A, Hall BM, Qualman SJ, Chandler DS, Croce CM, Guttridge DC (2008) NF-kappaB-YY1-miR-29 regulatory circuitry in skeletal myogenesis and rhabdomyosarcoma. Cancer Cell 14:369–381

    Article  PubMed  CAS  Google Scholar 

  48. Xiong Y, Fang JH, Yun JP, Yang J, Zhang Y, Jia WH, Zhuang SM (2010) Effects of microRNA-29 on apoptosis, tumorigenicity, and prognosis of hepatocellular carcinoma. Hepatol 51:836–845

    CAS  Google Scholar 

  49. Zhao JJ, Lin J, Lwin T, Yang H, Guo J, Kong W, Dessureault S, Moscinski LC, Rezania D, Dalton WS, Sotomayor E, Tao J, Cheng JQ (2010) microRNA expression profile and identification of miR-29 as a prognostic marker and pathogenetic factor by targeting CDK6 in mantle cell lymphoma. Blood 115:2630–2639

    Article  PubMed  CAS  Google Scholar 

  50. He L, He X, Lim LP, de Stanchina E, Xuan Z, Liang Y, Xue W, Zender L, Magnus J, Ridzon D, Jackson AL, Linsley PS, Chen C, Lowe SW, Cleary MA, Hannon GJ (2007) A microRNA component of the p53 tumour suppressor network. Nature 447:1130–1134

    Article  PubMed  CAS  Google Scholar 

  51. Tarasov V, Jung P, Verdoodt B, Lodygin D, Epanchintsev A, Menssen A, Meister G, Hermeking H (2007) Differential regulation of microRNAs by p53 revealed by massively parallel sequencing: miR-34a is a p53 target that induces apoptosis and G1-arrest. Cell Cycle 6:1586–1593

    Article  PubMed  CAS  Google Scholar 

  52. Sun F, Fu H, Liu Q, Tie Y, Zhu J, Xing R, Sun Z, Zheng X (2008) Downregulation of CCND1 and CDK6 by miR-34a induces cell cycle arrest. FEBS Lett 582:1564–1568

    Article  PubMed  CAS  Google Scholar 

  53. Corney DC, Flesken-Nikitin A, Godwin AK, Wang W, Nikitin AY (2007) MicroRNA-34b and MicroRNA-34c are targets of p53 and cooperate in control of cell proliferation and adhesion-independent growth. Cancer Res 67:8433–8438

    Article  PubMed  CAS  Google Scholar 

  54. Braun CJ, Zhang X, Savelyeva I, Wolff S, Moll UM, Schepeler T, Orntoft TF, Andersen CL, Dobbelstein M (2008) p53-Responsive micrornas 192 and 215 are capable of inducing cell cycle arrest. Cancer Res 68:10094–10104

    Article  PubMed  CAS  Google Scholar 

  55. Si ML, Zhu S, Wu H, Lu Z, Wu F, Mo YY (2007) miR-21-mediated tumor growth. Oncogene 26:2799–2803

    Article  PubMed  CAS  Google Scholar 

  56. Frankel LB, Christoffersen NR, Jacobsen A, Lindow M, Krogh A, Lund AH (2008) Programmed cell death 4 (PDCD4) is an important functional target of the microRNA miR-21 in breast cancer cells. J Biol Chem 283:1026–1033

    Article  PubMed  CAS  Google Scholar 

  57. Meng F, Henson R, Wehbe-Janek H, Ghoshal K, Jacob ST, Patel T (2007) MicroRNA-21 regulates expression of the PTEN tumor suppressor gene in human hepatocellular cancer. Gastroenterology 133:647–658

    Article  PubMed  CAS  Google Scholar 

  58. Zhu S, Si ML, Wu H, Mo YY (2007) MicroRNA-21 targets the tumor suppressor gene tropomyosin 1 (TPM1). J Biol Chem 282:14328–14336

    Article  PubMed  CAS  Google Scholar 

  59. Scott GK, Mattie MD, Berger CE, Benz SC, Benz CC (2006) Rapid alteration of microRNA levels by histone deacetylase inhibition. Cancer Res 66:1277–1281

    Article  PubMed  CAS  Google Scholar 

  60. Mertens-Talcott SU, Chintharlapalli S, Li X, Safe S (2007) The oncogenic microRNA-27a targets genes that regulate specificity protein transcription factors and the G2-M checkpoint in MDA-MB-231 breast cancer cells. Cancer Res 67:11001–11011

    Article  PubMed  CAS  Google Scholar 

  61. 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 285:17869–17879

    Article  PubMed  CAS  Google Scholar 

  62. 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 39:167–169

    Article  PubMed  CAS  Google Scholar 

  63. 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 Natl Acad Sci USA 104:16170–16175

    Article  PubMed  CAS  Google Scholar 

  64. Al-Hajj M, Wicha MS, Benito-Hernandez A, Morrison SJ, Clarke MF (2003) Prospective identification of tumorigenic breast cancer cells. Proc Natl Acad Sci USA 100:3983–3988

    Article  PubMed  CAS  Google Scholar 

  65. Gupta PB, Chaffer CL, et al (2009) Cancer stem cells: mirage or reality? Nature Med 15:1010–1012

    Article  PubMed  CAS  Google Scholar 

  66. Singh SK, Clarke ID, Terasaki M, Bonn VE, Hawkins C, Squire J, Dirks PB (2003) Identification of a cancer stem cell in human brain tumors. Cancer Res 63:5821–5828

    PubMed  CAS  Google Scholar 

  67. Lapidot T, Sirard C, Vormoor J, Murdoch B, Hoang T, Caceres-Cortes J, Minden M, Paterson B, Caligiuri MA, Dick JE (1994) A cell initiating human acute myeloid leukaemia after transplantation into SCID mice. Nature 367:645–648

    Article  PubMed  CAS  Google Scholar 

  68. Ricci-Vitiani L, Lombardi DG, Pilozzi E, Biffoni M, Todaro M, Peschle C, De Maria R (2007) Identification and expansion of human colon-cancer-initiating cells. Nature 445:111–115

    Article  PubMed  CAS  Google Scholar 

  69. Li C, Heidt DG, Dalerba P, Burant CF, Zhang L, Adsay V, Wicha M, Clarke MF, Simeone DM (2007) Identification of pancreatic cancer stem cells. Cancer Res 67:1030–1037

    Article  PubMed  CAS  Google Scholar 

  70. Ginestier C, Hur MH, Charafe-Jauffret E, Monville F, Dutcher J, Brown M, Jacquemier J, Viens P, Kleer CG, Liu S, Schott A, Hayes D, Birnbaum D, Wicha MS, Dontu G (2007) ALDH1 is a marker of normal and malignant human mammary stem cells and a predictor of poor clinical outcome. Cell Stem Cell 1:555–567

    Article  PubMed  CAS  Google Scholar 

  71. Velasco-Velázquez MA, Yu Z, Jiao X, et al (2009) Cancer stem cells and the cell cycle: targeting the drive behind breast cancer. Expert Rev Anticancer Ther 9:275–9

    Article  PubMed  Google Scholar 

  72. Qian S, Ding JY, Xie R, An JH, Ao XJ, Zhao ZG, Sun JG, Duan YZ, Chen ZT, Zhu B (2008) MicroRNA expression profile of bronchioalveolar stem cells from mouse lung. Biochem Biophys Res Commun 377:668–673

    Article  PubMed  CAS  Google Scholar 

  73. Shimono Y, Zabala M, Cho RW, Lobo N, Dalerba P, Qian D, Diehn M, Liu H, Panula SP, Chiao E, Dirbas FM, Somlo G, Pera RA, Lao K, Clarke MF (2009) Downregulation of miRNA-200c links breast cancer stem cells with normal stem cells. Cell 138:592–603

    Article  PubMed  CAS  Google Scholar 

  74. Gregory PA, Bert AG, Paterson EL, Barry SC, Tsykin A, Farshid G, Vadas MA, Khew-Goodall Y, Goodall GJ (2008) The miR-200 family and miR-205 regulate epithelial to mesenchymal transition by targeting ZEB1 and SIP1. Nat Cell Biol 10:593–601

    Article  PubMed  CAS  Google Scholar 

  75. Huang Q, Gumireddy K, Schrier M, le Sage C, Nagel R, Nair S, Egan DA, Li A, Huang G, Klein-Szanto AJ, Gimotty PA, Katsaros D, Coukos G, Zhang L, Pure E, Agami R (2008) The microRNAs miR-373 and miR-520c promote tumour invasion and metastasis. Nat Cell Biol 10:202–210

    Article  PubMed  CAS  Google Scholar 

  76. Yu Z, Willmarth NE, Zhou J, Katiyar S, Wang M, Liu Y, McCue PA, Quong AA, Lisanti MP, Pestell RG (2010) MicroRNA 17/20 inhibits cellular invasion and tumor metastasis in breast cancer by heterotypic signaling. Proc Natl Acad Sci USA 107:8231–8236

    Article  PubMed  CAS  Google Scholar 

  77. 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 435:834–838

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  79. Bader AG, Brown D, Winkler M (2010) The promise of microRNA replacement therapy. Cancer Res 70:7027–7030

    Article  PubMed  CAS  Google Scholar 

  80. Trang P, Medina PP, Wiggins JF, Ruffino L, Kelnar K, Omotola M, Homer R, Brown D, Bader AG, Weidhaas JB, Slack FJ (2010) Regression of murine lung tumors by the let-7 microRNA. Oncogene 29:1580–1587

    Article  PubMed  CAS  Google Scholar 

  81. Wiggins JF, Ruffino L, Kelnar K, Omotola M, Patrawala L, Brown D, Bader AG (2010) Development of a lung cancer therapeutic based on the tumor suppressor microRNA-34. Cancer Res 70:5923–5930

    Article  PubMed  CAS  Google Scholar 

  82. 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 137:1005–1017

    Article  PubMed  CAS  Google Scholar 

  83. Ebert MS, Neilson JR, Sharp PA (2007) MicroRNA sponges: competitive inhibitors of small RNAs in mammalian cells. Nat Methods 4:721–726

    Article  PubMed  CAS  Google Scholar 

  84. Choi WY, Giraldez AJ, Schier AF (2007) Target protectors reveal dampening and balancing of Nodal agonist and antagonist by miR-430. Science 318:271–274

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

This work was supported in part by awards from National Institutes of Health [R01CA70896, R01CA75503, and R01CA86072 to R.G.P.]. Work conducted at the Kimmel Cancer Center was supported by the NIH Cancer Center Core grant [P30CA56036 to R.G.P.]. This project is supported by a generous grant from the Dr. Ralph and Marian C. Falk Medical Research Trust, and was funded and supported in part by a grant from the Pennsylvania Department of Health. The Department specifically disclaims responsibility for any analyses, interpretations or conclusions.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Zuoren Yu Ph.D. .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2013 Springer Science+Business Media Dordrecht

About this chapter

Cite this chapter

Yu, Z., Tozeren, A., Pestell, R. (2013). Function of miRNAs in Tumor Cell Proliferation. In: Alahari, S. (eds) MicroRNA in Cancer. Springer, Dordrecht. https://doi.org/10.1007/978-94-007-4655-8_2

Download citation

Publish with us

Policies and ethics