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Journal of Gastrointestinal Surgery

Published in:

01-07-2009 | Review Article

Small RNA: A Large Contributor to Carcinogenesis?

Authors: Imran Bhatti, Andrew Lee, Jonathan Lund, Michael Larvin

Published in: Journal of Gastrointestinal Surgery | Issue 7/2009

Abstract

Introduction

Homeostasis in normal tissue includes balancing cell proliferation and apoptosis (programmed cell death). Mutations in proto-oncogenes or tumor suppressor genes may lead to disruption of normal cellular function, uncontrolled cell proliferation, and subsequent carcinogenesis.

Discussion

Micro-RNAs (miRNAs) are short (19–24 nucleotide) noncoding RNA sequences that inhibit protein translation and can cause the degradation of subsequent messenger RNA, thus playing an important role in the regulation of gene expression. Aberrant expression of miRNAs has been shown to inhibit tumor suppressor genes or inappropriately activate oncogenes initiating the cancer process. Unique miRNA expression profiles have been found in different cancer types at different stages, suggesting a possible diagnostic application. This review summarizes the current evidence supporting a link between aberrant miRNA expression and carcinogenesis and its possible role in improving diagnosis and treatment of cancers, particularly of gastrointestinal origin.

Wightman B, Ha I, Ruvkun G. Posttranscriptional regulation of the heterochronic gene lin-14 by lin-4 mediates temporal pattern formation in C. elegans. Cell 1993;75(5):855–862. doi:10.1016/0092-8674(93)90530-4.PubMedCrossRef

Tili E, Michaille JJ, Calin GA. Expression and function of micro-RNAs in immune cells during normal or disease state. Int J Med Sci 2008;5(2):73–79.PubMed

Ambros V. The functions of animal microRNAs. Nature 2004;431(7006):350–355. doi:10.1038/nature02871.PubMedCrossRef

Lee RC, Feinbaum RL, Ambros V. The C. elegans heterochronic gene lin-4 encodes small RNAs with antisense complementarity to lin-14. Cell 1993;75(5):843–854. doi:10.1016/0092-8674(93)90529-Y.PubMedCrossRef

Griffiths-Jones S, Grocock RJ, van Dongen S, Bateman A, Enright AJ. miRBase: microRNA sequences, targets and gene nomenclature. Nucleic Acids Res 2006;34(Database issue):D140–D144. doi:10.1093/nar/gkj112.PubMedCrossRef

Stahlhut Espinosa CE, Slack FJ. The role of microRNAs in cancer. Yale J Biol Med 2006;79(3-4):131–140.PubMed

Borchert GM, Lanier W, Davidson BL. RNA polymerase III transcribes human microRNAs. Nat Struct Mol Biol 2006;13(12):1097–1101. doi:10.1038/nsmb1167.PubMedCrossRef

Preall JB, He Z, Gorra JM, Sontheimer EJ. Short interfering RNA strand selection is independent of dsRNA processing polarity during RNAi in Drosophila. Curr Biol 2006;16(5):530–535. doi:10.1016/j.cub.2006.01.061.PubMedCrossRef

Hammond SM, Bernstein E, Beach D, Hannon GJ. An RNA-directed nuclease mediates post-transcriptional gene silencing in Drosophila cells. Nature 2000;404(6775):293–296. doi:10.1038/35005107.PubMedCrossRef

10.

Papagiannakopoulos T, Kosik KS. MicroRNAs: regulators of oncogenesis and stemness. BMC Med 2008;6:15. doi:10.1186/1741-7015-6-15.PubMedCrossRef

11.

Filipowicz W, Bhattacharyya SN, Sonenberg N. Mechanisms of post-transcriptional regulation by microRNAs: are the answers in sight? Nat Rev Genet 2008;9(2):102–114. doi:10.1038/nrg2290.PubMedCrossRef

12.

Hammond SM, Boettcher S, Caudy AA, Kobayashi R, Hannon GJ. Argonaute2, a link between genetic and biochemical analyses of RNAi. Science. 2001;293(5532):1146–1150. doi:10.1126/science.1064023.PubMedCrossRef

13.

Mourelatos Z, Dostie J, Paushkin S, Sharma A, Charroux B, Abel L et al. miRNPs: a novel class of ribonucleoproteins containing numerous microRNAs. Genes Dev 2002;16(6):720–728. doi:10.1101/gad.974702.PubMedCrossRef

14.

Ingelfinger D, Arndt-Jovin DJ, Luhrmann R, Achsel T. The human LSm1-7 proteins colocalize with the mRNA-degrading enzymes Dcp1/2 and Xrnl in distinct cytoplasmic foci. RNA 2002;8(12):1489–1501.PubMed

15.

van Dijk E, Cougot N, Meyer S, Babajko S, Wahle E, Seraphin B. Human Dcp2: a catalytically active mRNA decapping enzyme located in specific cytoplasmic structures. EMBO J 2002;21(24):6915–6924. doi:10.1093/emboj/cdf678.PubMedCrossRef

16.

Kong YW, Cannell IG, de Moor CH, Hill K, Garside PG, Hamilton TL et al. The mechanism of micro-RNA-mediated translation repression is determined by the promoter of the target gene. Proc Natl Acad Sci U S A 2008;105(26):8866–8871. doi:10.1073/pnas.0800650105.PubMedCrossRef

17.

Vasudevan S, Tong Y, Steitz JA. Switching from repression to activation: microRNAs can up-regulate translation. Science 2007;318(5858):1931–1934. doi:10.1126/science.1149460.PubMedCrossRef

18.

Bird A. Perceptions of epigenetics. Nature 2007;447(7143):396–398. doi:10.1038/nature05913.PubMedCrossRef

19.

Willingham AT, Gingeras TR. TUF love for “junk” DNA. Cell 2006;125(7):1215–1220. doi:10.1016/j.cell.2006.06.009.PubMedCrossRef

20.

Jackson AL, Linsley PS. Noise amidst the silence: off-target effects of siRNAs? Trends Genet 2004;20(11):521–524. doi:10.1016/j.tig.2004.08.006.PubMedCrossRef

21.

Calin GA, Sevignani C, Dumitru CD, Hyslop T, Noch E, Yendamuri S et al. Human microRNA genes are frequently located at fragile sites and genomic regions involved in cancers. Proc Natl Acad Sci U S A 2004;101(9):2999–3004. doi:10.1073/pnas.0307323101.PubMedCrossRef

22.

Calin GA, Croce CM. MicroRNA signatures in human cancers. Nat Rev Cancer 2006;6(11):857–866. doi:10.1038/nrc1997.PubMedCrossRef

23.

Lu J, Getz G, Miska EA, Alvarez-Saavedra E, Lamb J, Peck D et al. MicroRNA expression profiles classify human cancers. Nature 2005;435(7043):834–838. doi:10.1038/nature03702.PubMedCrossRef

24.

Bloomston M, Frankel WL, Petrocca F, Volinia S, Alder H, Hagan JP et al. MicroRNA expression patterns to differentiate pancreatic adenocarcinoma from normal pancreas and chronic pancreatitis. JAMA 2007;297(17):1901–1908. doi:10.1001/jama.297.17.1901.PubMedCrossRef

25.

Calin GA, Dumitru CD, Shimizu M, Bichi R, Zupo S, Noch E et al. 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 2002;99(24):15524–15529. doi:10.1073/pnas.242606799.PubMedCrossRef

26.

Sanchez-Beato M, Sanchez-Aguilera A, Piris MA. Cell cycle deregulation in B-cell lymphomas. Blood 2003;101(4):1220–1235. doi:10.1182/blood-2002-07-2009.PubMedCrossRef

27.

Cimmino A, Calin GA, Fabbri M, Iorio MV, Ferracin M, Shimizu M et al. miR-15 and miR-16 induce apoptosis by targeting BCL2. Proc Natl Acad Sci U S A 2005;102(39):13944–13949. doi:10.1073/pnas.0506654102.PubMedCrossRef

28.

Johnson SM, Grosshans H, Shingara J, Byrom M, Jarvis R, Cheng A et al. RAS is regulated by the let-7 microRNA family. Cell 2005;120(5):635–647. doi:10.1016/j.cell.2005.01.014.PubMedCrossRef

29.

Bos JL. ras oncogenes in human cancer: a review. Cancer Res 1989;49(17):4682–4689.PubMed

30.

Bommer GT, Gerin I, Feng Y, Kaczorowski AJ, Kuick R, Love RE et al. p53-mediated activation of miRNA34 candidate tumor-suppressor genes. Curr Biol 2007;17(15):1298–1307. doi:10.1016/j.cub.2007.06.068.PubMedCrossRef

31.

Raver-Shapira N, Marciano E, Meiri E, Spector Y, Rosenfeld N, Moskovits N et al. Transcriptional activation of miR-34a contributes to p53-mediated apoptosis. Mol Cell 2007;26(5):731–743. doi:10.1016/j.molcel.2007.05.017.PubMedCrossRef

32.

Raver-Shapira N, Oren M. Tiny actors, great roles: microRNAs in p53’s service. Cell Cycle 2007;6(21):2656–2661.PubMed

33.

Pelengaris S, Khan M, Evan GI. Suppression of Myc-induced apoptosis in beta cells exposes multiple oncogenic properties of Myc and triggers carcinogenic progression. Cell 2002;109(3):321–334. doi:10.1016/S0092-8674(02)00738-9.PubMedCrossRef

34.

Kluiver J, Haralambieva E, de Jong D, Blokzijl T, Jacobs S, Kroesen BJ et al. Lack of BIC and microRNA miR-155 expression in primary cases of Burkitt lymphoma. Genes Chromosomes Cancer 2006;45(2):147–153. doi:10.1002/gcc.20273.PubMedCrossRef

35.

Metzler M, Wilda M, Busch K, Viehmann S, Borkhardt A. High expression of precursor microRNA-155/BIC RNA in children with Burkitt lymphoma. Genes Chromosomes Cancer 2004;39(2):167–169. doi:10.1002/gcc.10316.PubMedCrossRef

36.

Gironella M, Seux M, Xie MJ, Cano C, Tomasini R, Gommeaux J et al. Tumor protein 53-induced nuclear protein 1 expression is repressed by miR-155, and its restoration inhibits pancreatic tumor development. Proc Natl Acad Sci U S A 2007;104(41):16170–16175. doi:10.1073/pnas.0703942104.PubMedCrossRef

37.

Rodriguez A, Vigorito E, Clare S, Warren MV, Couttet P, Soond DR et al. Requirement of bic/microRNA-155 for normal immune function. Science 2007;316(5824):608–611. doi:10.1126/science.1139253.PubMedCrossRef

38.

Voorhoeve PM, le Sage C, Schrier M, Gillis AJ, Stoop H, Nagel R et al. A genetic screen implicates miRNA-372 and miRNA-373 as oncogenes in testicular germ cell tumors. Cell 2006;124(6):1169–1181. doi:10.1016/j.cell.2006.02.037.PubMedCrossRef

39.

Ota A, Tagawa H, Karnan S, Tsuzuki S, Karpas A, Kira S et al. Identification and characterization of a novel gene, C13orf25, as a target for 13q31-q32 amplification in malignant lymphoma. Cancer Res 2004;64(9):3087–3095. doi:10.1158/0008-5472.CAN-03-3773.PubMedCrossRef

40.

He L, Thomson JM, Hemann MT, Hernando-Monge E, Mu D, Goodson S et al. A microRNA polycistron as a potential human oncogene. Nature 2005;435(7043):828–833. doi:10.1038/nature03552.PubMedCrossRef

41.

Hayashita Y, Osada H, Tatematsu Y, Yamada H, Yanagisawa K, Tomida S et al. A polycistronic microRNA cluster, miR-17-92, is overexpressed in human lung cancers and enhances cell proliferation. Cancer Res 2005;65(21):9628–9632. doi:10.1158/0008-5472.CAN-05-2352.PubMedCrossRef

42.

Lewis BP, Shih IH, Jones-Rhoades MW, Bartel DP, Burge CB. Prediction of mammalian microRNA targets. Cell 2003;115(7):787–798. doi:10.1016/S0092-8674(03)01018-3.PubMedCrossRef

43.

Lu Y, Thomson JM, Wong HY, Hammond SM, Hogan BL. Transgenic over-expression of the microRNA miR-17-92 cluster promotes proliferation and inhibits differentiation of lung epithelial progenitor cells. Dev Biol 2007;310(2):442–453. doi:10.1016/j.ydbio.2007.08.007.PubMedCrossRef

44.

O’Donnell KA, Wentzel EA, Zeller KI, Dang CV, Mendell JT. c-Myc-regulated microRNAs modulate E2F1 expression. Nature 2005;435(7043):839–843. doi:10.1038/nature03677.PubMedCrossRef

45.

Cheng AM, Byrom MW, Shelton J, Ford LP. Antisense inhibition of human miRNAs and indications for an involvement of miRNA in cell growth and apoptosis. Nucleic Acids Res 2005;33(4):1290–1297. doi:10.1093/nar/gki200.PubMedCrossRef

46.

Chan JA, Krichevsky AM, Kosik KS. MicroRNA-21 is an antiapoptotic factor in human glioblastoma cells. Cancer Res 2005;65(14):6029–6033. doi:10.1158/0008-5472.CAN-05-0137.PubMedCrossRef

47.

Meng F, Henson R, Wehbe-Janek H, Ghoshal K, Jacob ST, Patel T. MicroRNA-21 regulates expression of the PTEN tumor suppressor gene in human hepatocellular cancer. Gastroenterology 2007;133(2):647–658. doi:10.1053/j.gastro.2007.05.022.PubMedCrossRef

48.

Enright AJ, John B, Gaul U, Tuschl T, Sander C, Marks DS. MicroRNA targets in Drosophila. Genome Biol 2003;5(1):R1. doi:10.1186/gb-2003-5-1-r1.PubMedCrossRef

49.

Kumar MS, Lu J, Mercer KL, Golub TR, Jacks T. Impaired microRNA processing enhances cellular transformation and tumorigenesis. Nat Genet 2007;39(5):673–677. doi:10.1038/ng2003.PubMedCrossRef

50.

Ma L, Teruya-Feldstein J, Weinberg RA. Tumour invasion and metastasis initiated by microRNA-10b in breast cancer. Nature 2007;449(7163):682–688. doi:10.1038/nature06174.PubMedCrossRef

51.

Blenkiron C, Goldstein LD, Thorne NP, Spiteri I, Chin SF, Dunning MJ et al. MicroRNA expression profiling of human breast cancer identifies new markers of tumor subtype. Genome Biol 2007;8(10):R214. doi:10.1186/gb-2007-8-10-r214.PubMedCrossRef

52.

Calin GA, Ferracin M, Cimmino A, Di Leva G, Shimizu M, Wojcik SE et al. A MicroRNA signature associated with prognosis and progression in chronic lymphocytic leukemia. N Engl J Med 2005;353(17):1793–1801. doi:10.1056/NEJMoa050995.PubMedCrossRef

53.

Feber A, Xi L, Luketich JD, Pennathur A, Landreneau RJ, Wu M et al. MicroRNA expression profiles of esophageal cancer. J Thorac Cardiovasc Surg 2008;135(2):255–260. discussion 60doi:10.1016/j.jtcvs.2007.08.055.PubMedCrossRef

54.

Guo Y, Chen Z, Zhang L, Zhou F, Shi S, Feng X et al. Distinctive microRNA profiles relating to patient survival in esophageal squamous cell carcinoma. Cancer Res 2008;68(1):26–33. doi:10.1158/0008-5472.CAN-06-4418.PubMedCrossRef

55.

Chan SH, Wu CW, Li AF, Chi CW, Lin WC. miR-21 microRNA expression in human gastric carcinomas and its clinical association. Anticancer Res 2008;28(2A):907–911.PubMed

56.

Motoyama K, Inoue H, Nakamura Y, Uetake H, Sugihara K, Mori M. Clinical significance of high mobility group A2 in human gastric cancer and its relationship to let-7 microRNA family. Clin Cancer Res 2008;14(8):2334–2340. doi:10.1158/1078-0432.CCR-07-4667.PubMedCrossRef

57.

Lee EJ, Gusev Y, Jiang J, Nuovo GJ, Lerner MR, Frankel WL et al. Expression profiling identifies microRNA signature in pancreatic cancer. Int J Cancer 2007;120(5):1046–1054. doi:10.1002/ijc.22394.PubMedCrossRef

58.

Poliseno L, Tuccoli A, Mariani L, Evangelista M, Citti L, Woods K et al. MicroRNAs modulate the angiogenic properties of HUVECs. Blood 2006;108(9):3068–3071. doi:10.1182/blood-2006-01-012369.PubMedCrossRef

59.

Dillhoff M, Liu J, Frankel W, Croce C, Bloomston M. MicroRNA-21 is overexpressed in pancreatic cancer and a potential predictor of survival. J Gastrointest Surg 2008;12:2171–2176.PubMedCrossRef

60.

Schetter AJ, Leung SY, Sohn JJ, Zanetti KA, Bowman ED, Yanaihara N et al. MicroRNA expression profiles associated with prognosis and therapeutic outcome in colon adenocarcinoma. JAMA 2008;299(4):425–436. doi:10.1001/jama.299.4.425.PubMedCrossRef

61.

Yaguang Xi AF, Minchen C et al. Prognostic values of microRNAs in colorectal cancer. Biomark Insights 2006;2:113–121.PubMed

62.

Nakajima G, Hayashi K, Xi Y, Kudo K, Uchida K, Takasaki K et al. Non-coding MicroRNAs hsa-let-7g and hsa-miR-181b are Associated with chemoresponse to S-1 in colon cancer. Cancer Genomics Proteomics 2006;3(5):317–324.PubMed

63.

Verghese ET, Hanby AM, Speirs V, Hughes TA. Small is beautiful: microRNAs and breast cancer—where are we now? J Pathol 2008;215(3):214–221. doi:10.1002/path.2359.PubMedCrossRef

64.

Mattie MD, Benz CC, Bowers J, Sensinger K, Wong L, Scott GK et al. Optimized high-throughput microRNA expression profiling provides novel biomarker assessment of clinical prostate and breast cancer biopsies. Mol Cancer 2006;5:24. doi:10.1186/1476-4598-5-24.PubMedCrossRef

65.

Xiao B, Guo J, Miao Y, Jiang Z, Huan R, Zhang Y et al. Detection of miR-106a in gastric carcinoma and its clinical significance. Clin Chim Acta 2008;400:97–102.PubMedCrossRef

66.

Costinean S, Zanesi N, Pekarsky Y, Tili E, Volinia S, Heerema N et al. Pre-B cell proliferation and lymphoblastic leukemia/high-grade lymphoma in E(mu)-miR155 transgenic mice. Proc Natl Acad Sci U S A 2006;103(18):7024–7029. doi:10.1073/pnas.0602266103.PubMedCrossRef

67.

Roldo C, Missiaglia E, Hagan JP, Falconi M, Capelli P, Bersani S et al. MicroRNA expression abnormalities in pancreatic endocrine and acinar tumors are associated with distinctive pathologic features and clinical behavior. J Clin Oncol 2006;24(29):4677–4684. doi:10.1200/JCO.2005.05.5194.PubMedCrossRef

68.

Huang Q, Gumireddy K, Schrier M, le Sage C, Nagel R, Nair S et al. The microRNAs miR-373 and miR-520c promote tumour invasion and metastasis. Nat Cell Biol 2008;10(2):202–210. doi:10.1038/ncb1681.PubMedCrossRef

69.

Hay ED. The mesenchymal cell, its role in the embryo, and the remarkable signaling mechanisms that create it. Dev Dyn 2005;233(3):706–720. doi:10.1002/dvdy.20345.PubMedCrossRef

70.

Shook D, Keller R. Mechanisms, mechanics and function of epithelial–mesenchymal transitions in early development. Mech Dev 2003;120(11):1351–1383. doi:10.1016/j.mod.2003.06.005.PubMedCrossRef

71.

Thiery JP. Epithelial–mesenchymal transitions in tumour progression. Nat Rev Cancer 2002;2(6):442–454. doi:10.1038/nrc822.PubMedCrossRef

72.

Thiery JP, Sleeman JP. Complex networks orchestrate epithelial–mesenchymal transitions. Nat Rev Mol Cell Biol 2006;7(2):131–142. doi:10.1038/nrm1835.PubMedCrossRef

73.

Huber MA, Kraut N, Beug H. Molecular requirements for epithelial–mesenchymal transition during tumor progression. Curr Opin Cell Biol 2005;17(5):548–558. doi:10.1016/j.ceb.2005.08.001.PubMedCrossRef

74.

Becker KF, Rosivatz E, Blechschmidt K, Kremmer E, Sarbia M, Hofler H. Analysis of the E-cadherin repressor Snail in primary human cancers. Cells Tissues Organs 2007;185(1–3):204–212. doi:10.1159/000101321.PubMedCrossRef

75.

Kalluri R, Neilson EG. Epithelial–mesenchymal transition and its implications for fibrosis. J Clin Invest 2003;112(12):1776–1784.PubMed

76.

Hennig G, Behrens J, Truss M, Frisch S, Reichmann E, Birchmeier W. Progression of carcinoma cells is associated with alterations in chromatin structure and factor binding at the E-cadherin promoter in vivo. Oncogene 1995;11(3):475–484.PubMed

77.

Mello CC, Conte D Jr. Revealing the world of RNA interference. Nature 2004;431(7006):338–342. doi:10.1038/nature02872.PubMedCrossRef

78.

Krutzfeldt J, Rajewsky N, Braich R, Rajeev KG, Tuschl T, Manoharan M et al. Silencing of microRNAs in vivo with ‘antagomirs’. Nature 2005;438(7068):685–689. doi:10.1038/nature04303.PubMedCrossRef

79.

Krutzfeldt J, Kuwajima S, Braich R, Rajeev KG, Pena J, Tuschl T et al. Specificity, duplex degradation and subcellular localization of antagomirs. Nucleic Acids Res 2007;35(9):2885–2892. doi:10.1093/nar/gkm024.PubMedCrossRef

80.

Xia L, Zhang D, Du R, Pan Y, Zhao L, Sun S et al. miR-15b and miR-16 modulate multidrug resistance by targeting BCL2 in human gastric cancer cells. Int J Cancer 2008;123(2):372–379. doi:10.1002/ijc.23501.PubMedCrossRef

81.

Si ML, Zhu S, Wu H, Lu Z, Wu F, Mo YY. miR-21-mediated tumor growth. Oncogene 2007;26(19):2799–2803. doi:10.1038/sj.onc.1210083.PubMedCrossRef

82.

Sorrentino A, Liu CG, Addario A, Peschle C, Scambia G, Ferlini C. Role of microRNAs in drug-resistant ovarian cancer cells. Gynecol Oncol 2008;111:478–486.PubMedCrossRef

Title: Small RNA: A Large Contributor to Carcinogenesis?
Authors: Imran Bhatti
Andrew Lee
Jonathan Lund
Michael Larvin
Publication date: 01-07-2009
Publisher: Springer-Verlag
Published in: Journal of Gastrointestinal Surgery / Issue 7/2009
Print ISSN: 1091-255X
Electronic ISSN: 1873-4626
DOI: https://doi.org/10.1007/s11605-009-0887-6

At a glance: The STEP trials

Springer Medicine

Small RNA: A Large Contributor to Carcinogenesis?

Abstract

Introduction

Discussion

At a glance: The STEP trials

Springer Medicine

Abstract

Introduction

Discussion

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