Therapeutic Opportunities for Targeting microRNAs in Cancer

  • Molly Taylor Oncology iMed, AstraZeneca R&D, Alderley Park, Macclesfield SK10 4TG, UK
  • William Sciemann Case Comprehensive Cancer Center, Case Western Reserve University, Wolstein Research Building, Cleveland, OH 44106, USA
Keywords: Antisense oligonucleotides, Biomarkers, Chemotherapeutics, Locked nucleic acids, MetastamiR, Metastasis, microRNA, OncomiR

Abstract

MicroRNAs (miRNAs) are small noncoding RNAs that can function as either powerful tumor promoters or suppressors in numerous types of cancer. The ability of miRs to target multiple genes and biological signaling pathways has created intense interest in their potential clinical utility as predictive and diagnostic biomarkers, and as innovative therapeutic agents. Recently, accumulating preclinical studies have illustrated the feasibility of slowing tumor progression by either overexpressing tumor suppressive miRNAs, or by neutralizing the activities of oncogenic miRNAs in cell- and animal-based models of cancer. Here we highlight prominent miRNAs that may represent potential therapeutic targets in human malignancies, as well as review current technologies available for inactivating or restoring miRNA activity in clinical settings.

Downloads

Download data is not yet available.

Author Biographies

Molly Taylor, Oncology iMed, AstraZeneca R&D, Alderley Park, Macclesfield SK10 4TG, UK

Molly A. Taylor is a Senior Scientist at AstraZeneca in Cambridge, UK. She received her B.A. in Molecular, Cellular, and Developmental Biology from the University of Colorado, Boulder. After which, she spent two years working National Jewish Medical and Research Center defining the role of gamma-delta T-cell subsets in immune response to infection. She went on to obtain her PhD from Case Western Reserve University, in the laboratory of William P. Schiemann, where she investigated the role of the tumor microenvironment and microRNA expression on TGF-beta-mediated breast cancer progression. After completing her PhD, she joined the AstraZeneca postdoc programme where she investigated the use of microRNAs as biomarkers of intrinsic and acquired resistance. Taylor is currently working on oncology biomarkers as Senior Scientist in the oncology bioscience group at AstraZeneca.

William Sciemann, Case Comprehensive Cancer Center, Case Western Reserve University, Wolstein Research Building, Cleveland, OH 44106, USA

William P. Schiemann is the Goodman-Blum Professor in Cancer Research in the Case Comprehensive Cancer Center. Dr. Schiemann received his BS in Premedicine from the University of Nevada-Reno in 1990. After receiving his PhD in Pharmacology from the University of Washington in 1996, Dr. Schiemann joined the laboratory of Dr. Harvey F. Lodish at the Whitehead Institute for Biomedical Research and MIT, where he initiated studies of the “TGFß-Paradox” and its role in driving breast cancer metastasis and disease recurrence. In 2001, Dr. Schiemann expanded these analyses as an independent investigator, initially as an Assistant Professor at National Jewish Health (Denver, CO) and subsequently as an Associate Professor at the University of Colorado School of Medicine (Aurora, CO). In 2010, Dr. Schiemann moved his research program to Case Western Reserve University and its Comprehensive Cancer Center, wherein he continues to elucidate the molecular mechanisms that underlie breast cancer development, metastasis, and disease recurrence.

References

Siegel R, Ma J, Zou Z, Jemal A: Cancer statistics, 2014. CA Cancer J Clin. 2014, 64: 9-29. 10.3322/caac.21208.

PubMedGoogle Scholar

Li GW, Xie XS: Central dogma at the single-molecule level in living cells. Nature. 2011, 475: 308-315. 10.1038/nature10315.

PubMedCentralPubMedGoogle Scholar

Esteller M: Non-coding RNAs in human disease. Nat Rev Genet. 2011, 12: 861-874. 10.1038/nrg3074.

PubMedGoogle Scholar

Ling H, Fabbri M, Calin GA: MicroRNAs and other non-coding RNAs as targets for anticancer drug development. Nat Rev Drug Discov. 2013, 12: 847-865. 10.1038/nrd4140.

PubMedCentralPubMedGoogle Scholar

Garzon R, Marcucci G, Croce CM: Targeting microRNAs in cancer: rationale, strategies and challenges. Nat Rev Drug Discov. 2010, 9: 775-789. 10.1038/nrd3179.

PubMedCentralPubMedGoogle Scholar

Ambros V: The functions of animal microRNAs. Nature. 2004, 431: 350-355. 10.1038/nature02871.

PubMedGoogle Scholar

Ventura A, Jacks T: MicroRNAs and cancer: short RNAs go a long way. Cell. 2009, 136: 586-591. 10.1016/j.cell.2009.02.005.

PubMedCentralPubMedGoogle Scholar

Nicoloso MS, Spizzo R, Shimizu M, Rossi S, Calin GA: MicroRNAs–the micro steering wheel of tumour metastases. Nat Rev Cancer. 2009, 9: 293-302. 10.1038/nrc2619.

PubMedGoogle Scholar

Calin GA, Sevignani C, Dumitru CD, Hyslop T, Noch E, Yendamuri S, Shimizu M, Rattan S, Bullrich F, Negrini M, Croce CM: Human microRNA genes are frequently located at fragile sites and genomic regions involved in cancers. Proc Natl Acad Sci U S A. 2004, 101: 2999-3004. 10.1073/pnas.0307323101.

PubMedCentralPubMedGoogle Scholar

Mendell JT, Olson EN: MicroRNAs in stress signaling and human disease. Cell. 2012, 148: 1172-1187. 10.1016/j.cell.2012.02.005.

PubMedCentralPubMedGoogle Scholar

Leung AK, Sharp PA: MicroRNA functions in stress responses. Mol Cell. 2010, 40: 205-215. 10.1016/j.molcel.2010.09.027.

PubMedCentralPubMedGoogle Scholar

Janssen HL, Reesink HW, Lawitz EJ, Zeuzem S, Rodriguez-Torres M, Patel K, van der Meer AJ, Patick AK, Chen A, Zhou Y, Persson R, King BD, Kauppinen S, Levin AA, Hodges MR: Treatment of HCV infection by targeting microRNA. N Engl J Med. 2013, 368: 1685-1694. 10.1056/NEJMoa1209026.

PubMedGoogle Scholar

Winter J, Jung S, Keller S, Gregory RI, Diederichs S: Many roads to maturity: microRNA biogenesis pathways and their regulation. Nat Cell Biol. 2009, 11: 228-234. 10.1038/ncb0309-228.

PubMedGoogle Scholar

Trabucchi M, Briata P, Garcia-Mayoral M, Haase AD, Filipowicz W, Ramos A, Gherzi R, Rosenfeld MG: The RNA-binding protein KSRP promotes the biogenesis of a subset of microRNAs. Nature. 2009, 459: 1010-1014. 10.1038/nature08025.

PubMedCentralPubMedGoogle Scholar

Yi R, Qin Y, Macara IG, Cullen BR: Exportin-5 mediates the nuclear export of pre-microRNAs and short hairpin RNAs. Genes Dev. 2003, 17: 3011-3016. 10.1101/gad.1158803.

PubMedCentralPubMedGoogle Scholar

Hutvagner G, McLachlan J, Pasquinelli AE, Balint E, Tuschl T, Zamore PD: A cellular function for the RNA-interference enzyme Dicer in the maturation of the let-7 small temporal RNA. Science. 2001, 293: 834-838. 10.1126/science.1062961.

PubMedGoogle Scholar

Khvorova A, Reynolds A, Jayasena SD: Functional siRNAs and miRNAs exhibit strand bias. Cell. 2003, 115: 209-216. 10.1016/S0092-8674(03)00801-8.

PubMedGoogle Scholar

Blahna MT, Hata A: Regulation of miRNA biogenesis as an integrated component of growth factor signaling. Curr Opin Cell Biol. 2013, 25: 233-240. 10.1016/j.ceb.2012.12.005.

PubMedCentralPubMedGoogle Scholar

Sun X, Jiao X, Pestell TG, Fan C, Qin S, Mirabelli E, Ren H, Pestell RG: MicroRNAs and cancer stem cells: the sword and the shield. Oncogene. 2013, doi:10.1038/onc.2013.492. [Epub ahead of print]

Google Scholar

Davis BN, Hilyard AC, Lagna G, Hata A: SMAD proteins control DROSHA-mediated microRNA maturation. Nature. 2008, 454: 56-61. 10.1038/nature07086.

PubMedCentralPubMedGoogle Scholar

Davis BN, Hilyard AC, Nguyen PH, Lagna G, Hata A: Smad proteins bind a conserved RNA sequence to promote microRNA maturation by Drosha. Mol Cell. 2010, 39: 373-384. 10.1016/j.molcel.2010.07.011.

PubMedCentralPubMedGoogle Scholar

Piriyapongsa J, Jordan IK, Conley AB, Ronan T, Smalheiser NR: Transcription factor binding sites are highly enriched within microRNA precursor sequences. Biol Direct. 2011, 6: 61-10.1186/1745-6150-6-61.

PubMedCentralPubMedGoogle Scholar

Suzuki HI, Yamagata K, Sugimoto K, Iwamoto T, Kato S, Miyazono K: Modulation of microRNA processing by p53. Nature. 2009, 460: 529-533. 10.1038/nature08199.

PubMedGoogle Scholar

Zhang X, Wan G, Berger FG, He X, Lu X: The ATM kinase induces microRNA biogenesis in the DNA damage response. Mol Cell. 2011, 41: 371-383. 10.1016/j.molcel.2011.01.020.

PubMedCentralPubMedGoogle Scholar

Briata P, Lin WJ, Giovarelli M, Pasero M, Chou CF, Trabucchi M, Rosenfeld MG, Chen CY, Gherzi R: PI3K/AKT signaling determines a dynamic switch between distinct KSRP functions favoring skeletal myogenesis. Cell Death Differ. 2012, 19: 478-487. 10.1038/cdd.2011.117.

PubMedCentralPubMedGoogle Scholar

Paroo Z, Ye X, Chen S, Liu Q: Phosphorylation of the human microRNA-generating complex mediates MAPK/Erk signaling. Cell. 2009, 139: 112-122. 10.1016/j.cell.2009.06.044.

PubMedCentralPubMedGoogle Scholar

Roush S, Slack FJ: The let-7 family of microRNAs. Trends Cell Biol. 2008, 18: 505-516. 10.1016/j.tcb.2008.07.007.

PubMedGoogle Scholar

Yamagata K, Fujiyama S, Ito S, Ueda T, Murata T, Naitou M, Takeyama K, Minami Y, O’Malley BW, Kato S: Maturation of microRNA is hormonally regulated by a nuclear receptor. Mol Cell. 2009, 36: 340-347. 10.1016/j.molcel.2009.08.017.

PubMedGoogle Scholar

Shen J, Xia W, Khotskaya YB, Huo L, Nakanishi K, Lim SO, Du Y, Wang Y, Chang WC, Chen CH, Hsu JL, Wu Y, Lam YC, James BP, Liu X, Liu CG, Patel DJ, Hung MC: EGFR modulates microRNA maturation in response to hypoxia through phosphorylation of AGO2. Nature. 2013, 497: 383-387. 10.1038/nature12080.

PubMedCentralPubMedGoogle Scholar

Hanahan D, Weinberg RA: The hallmarks of cancer. Cell. 2000, 100: 57-70. 10.1016/S0092-8674(00)81683-9.

PubMedGoogle Scholar

Hanahan D, Weinberg RA: Hallmarks of cancer: the next generation. Cell. 2011, 144: 646-674. 10.1016/j.cell.2011.02.013.

PubMedGoogle Scholar

Chou J, Shahi P, Werb Z: microRNA-mediated regulation of the tumor microenvironment. Cell Cycle. 2013, 12 (20): 3262-3271. doi:10.4161/cc.26087. Epub 2013 Aug 26

PubMedCentralPubMedGoogle Scholar

Yates LA, Norbury CJ, Gilbert RJ: The long and short of microRNA. Cell. 2013, 153: 516-519. 10.1016/j.cell.2013.04.003.

PubMedGoogle Scholar

He L, Thomson JM, Hemann MT, Hernando-Monge E, Mu D, Goodson S, Powers S, Cordon-Cardo C, Lowe SW, Hannon GJ, Hammond SM: A microRNA polycistron as a potential human oncogene. Nature. 2005, 435: 828-833. 10.1038/nature03552.

PubMedCentralPubMedGoogle Scholar

Tanzer A, Stadler PF: Molecular evolution of a microRNA cluster. J Mol Biol. 2004, 339: 327-335. 10.1016/j.jmb.2004.03.065.

PubMedGoogle Scholar

Ota A, Tagawa H, Karnan S, Tsuzuki S, Karpas A, Kira S, Yoshida Y, Seto M: Identification and characterization of a novel gene, C13orf25, as a target for 13q31-q32 amplification in malignant lymphoma. Cancer Res. 2004, 64: 3087-3095. 10.1158/0008-5472.CAN-03-3773.

PubMedGoogle Scholar

Xiao C, Srinivasan L, Calado DP, Patterson HC, Zhang B, Wang J, Henderson JM, Kutok JL, Rajewsky K: Lymphoproliferative disease and autoimmunity in mice with increased miR-17-92 expression in lymphocytes. Nat Immunol. 2008, 9: 405-414. 10.1038/ni1575.

PubMedCentralPubMedGoogle Scholar

Koralov SB, Muljo SA, Galler GR, Krek A, Chakraborty T, Kanellopoulou C, Jensen K, Cobb BS, Merkenschlager M, Rajewsky N, Rajewsky K: Dicer ablation affects antibody diversity and cell survival in the B lymphocyte lineage. Cell. 2008, 132: 860-874. 10.1016/j.cell.2008.02.020.

PubMedGoogle Scholar

Ventura A, Young AG, Winslow MM, Lintault L, Meissner A, Erkeland SJ, Newman J, Bronson RT, Crowley D, Stone JR, Jaenisch R, Sharp PA, Jacks T: Targeted deletion reveals essential and overlapping functions of the miR-17 through 92 family of miRNA clusters. Cell. 2008, 132: 875-886. 10.1016/j.cell.2008.02.019.

PubMedCentralPubMedGoogle Scholar

Petrocca F, Visone R, Onelli MR, Shah MH, Nicoloso MS, de Martino I, Iliopoulos D, Pilozzi E, Liu CG, Negrini M, Cavazzini L, Volinia S, Alder H, Ruco LP, Baldassarre G, Croce CM, Vecchione A: E2F1-regulated microRNAs impair TGFbeta-dependent cell-cycle arrest and apoptosis in gastric cancer. Cancer Cell. 2008, 13: 272-286. 10.1016/j.ccr.2008.02.013.

PubMedGoogle Scholar

Ivanovska I, Ball AS, Diaz RL, Magnus JF, Kibukawa M, Schelter JM, Kobayashi SV, Lim L, Burchard J, Jackson AL, Linsley PS, Cleary MA: MicroRNAs in the miR-106b family regulate p21/CDKN1A and promote cell cycle progression. Mol Cell Biol. 2008, 28: 2167-2174. 10.1128/MCB.01977-07.

PubMedCentralPubMedGoogle Scholar

Dews M, Homayouni A, Yu D, Murphy D, Sevignani C, Wentzel E, Furth EE, Lee WM, Enders GH, Mendell JT, Thomas-Tikhonenko A: Augmentation of tumor angiogenesis by a Myc-activated microRNA cluster. Nat Genet. 2006, 38: 1060-1065. 10.1038/ng1855.

PubMedCentralPubMedGoogle Scholar

Smith AL, Iwanaga R, Drasin DJ, Micalizzi DS, Vartuli RL, Tan AC, Ford HL: The miR-106b-25 cluster targets Smad7, activates TGF-beta signaling, and induces EMT and tumor initiating cell characteristics downstream of Six1 in human breast cancer. Oncogene. 2012, 31: 5162-5171. 10.1038/onc.2012.11.

PubMedCentralPubMedGoogle Scholar

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

PubMedGoogle Scholar

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: A microRNA expression signature of human solid tumors defines cancer gene targets. Proc Natl Acad Sci U S A. 2006, 103: 2257-2261. 10.1073/pnas.0510565103.

PubMedCentralPubMedGoogle Scholar

Jazbutyte V, Thum T: MicroRNA-21: from cancer to cardiovascular disease. Curr Drug Targets. 2010, 11: 926-935. 10.2174/138945010791591403.

PubMedGoogle Scholar

Pan X, Wang ZX, Wang R: MicroRNA-21: a novel therapeutic target in human cancer. Cancer Biol Ther. 2010, 10: 1224-1232. 10.4161/cbt.10.12.14252.

PubMedGoogle Scholar

Qian B, Katsaros D, Lu L, Preti M, Durando A, Arisio R, Mu L, Yu H: High miR-21 expression in breast cancer associated with poor disease-free survival in early stage disease and high TGF-b1. Breast Cancer Res Treat. 2009, 117: 131-140. 10.1007/s10549-008-0219-7.

PubMedGoogle Scholar

Yang M, Shen H, Qiu C, Ni Y, Wang L, Dong W, Liao Y, Du J: High expression of miR-21 and miR-155 predicts recurrence and unfavourable survival in non-small cell lung cancer. Eur J Cancer. 2013, 49: 604-615. 10.1016/j.ejca.2012.09.031.

PubMedGoogle Scholar

Eis PS, Tam W, Sun L, Chadburn A, Li Z, Gomez MF, Lund E, Dahlberg JE: Accumulation of miR-155 and BIC RNA in human B cell lymphomas. Proc Natl Acad Sci U S A. 2005, 102: 3627-3632. 10.1073/pnas.0500613102.

PubMedCentralPubMedGoogle Scholar

Tam W, Hughes SH, Hayward WS, Besmer P: Avian bic, a gene isolated from a common retroviral site in avian leukosis virus-induced lymphomas that encodes a noncoding RNA, cooperates with c-myc in lymphomagenesis and erythroleukemogenesis. J Virol. 2002, 76: 4275-4286. 10.1128/JVI.76.9.4275-4286.2002.

PubMedCentralPubMedGoogle Scholar

Tili E, Croce CM, Michaille JJ: miR-155: on the crosstalk between inflammation and cancer. Int Rev Immunol. 2009, 28: 264-284. 10.1080/08830180903093796.

PubMedGoogle Scholar

Kong W, Yang H, He L, Zhao JJ, Coppola D, Dalton WS, Cheng JQ: MicroRNA-155 is regulated by the transforming growth factor b/Smad pathway and contributes to epithelial cell plasticity by targeting RhoA. Mol Cell Biol. 2008, 28: 6773-6784. 10.1128/MCB.00941-08.

PubMedCentralPubMedGoogle Scholar

Jiang S, Zhang HW, Lu MH, He XH, Li Y, Gu H, Liu MF, Wang ED: MicroRNA-155 functions as an OncomiR in breast cancer by targeting the suppressor of cytokine signaling 1 gene. Cancer Res. 2010, 70: 3119-3127. 10.1158/0008-5472.CAN-09-4250.

PubMedGoogle Scholar

Kong W, He L, Coppola M, Guo J, Esposito NN, Coppola D, Cheng JQ: MicroRNA-155 regulates cell survival, growth, and chemosensitivity by targeting FOXO3a in breast cancer. J Biol Chem. 2010, 285: 17869-17879. 10.1074/jbc.M110.101055.

PubMedCentralPubMedGoogle Scholar

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: 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: 15524-15529. 10.1073/pnas.242606799.

PubMedCentralPubMedGoogle Scholar

Dong JT, Boyd JC, Frierson HF: Loss of heterozygosity at 13q14 and 13q21 in high grade, high stage prostate cancer. Prostate. 2001, 49: 166-171. 10.1002/pros.1131.

PubMedGoogle Scholar

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: MiR-15a and miR-16-1 cluster functions in human leukemia. Proc Natl Acad Sci U S A. 2008, 105: 5166-5171. 10.1073/pnas.0800121105.

PubMedCentralPubMedGoogle Scholar

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: The miR-15a-miR-16-1 cluster controls prostate cancer by targeting multiple oncogenic activities. Nat Med. 2008, 14: 1271-1277. 10.1038/nm.1880.

PubMedGoogle Scholar

Reinhart BJ, Slack FJ, Basson M, Pasquinelli AE, Bettinger JC, Rougvie AE, Horvitz HR, Ruvkun G: The 21-nucleotide let-7 RNA regulates developmental timing in Caenorhabditis elegans. Nature. 2000, 403: 901-906. 10.1038/35002607.

PubMedGoogle Scholar

Takamizawa J, Konishi H, Yanagisawa K, Tomida S, Osada H, Endoh H, Harano T, Yatabe Y, Nagino M, Nimura Y, Mitsudomi T, Takahashi T: Reduced expression of the let-7 microRNAs in human lung cancers in association with shortened postoperative survival. Cancer Res. 2004, 64: 3753-3756. 10.1158/0008-5472.CAN-04-0637.

PubMedGoogle Scholar

Shi XB, Tepper CG, deVere White RW: Cancerous miRNAs and their regulation. Cell Cycle. 2008, 7: 1529-1538. 10.4161/cc.7.11.5977.

PubMedGoogle Scholar

Yu F, Yao H, Zhu P, Zhang X, Pan Q, Gong C, Huang Y, Hu X, Su F, Lieberman J, Song E: Let-7 regulates self renewal and tumorigenicity of breast cancer cells. Cell. 2007, 131: 1109-1123. 10.1016/j.cell.2007.10.054.

PubMedGoogle Scholar

Weidhaas JB, Babar I, Nallur SM, Trang P, Roush S, Boehm M, Gillespie E, Slack FJ: MicroRNAs as potential agents to alter resistance to cytotoxic anticancer therapy. Cancer Res. 2007, 67: 11111-11116. 10.1158/0008-5472.CAN-07-2858.

PubMedGoogle Scholar

Sampson VB, Rong NH, Han J, Yang Q, Aris V, Soteropoulos P, Petrelli NJ, Dunn SP, Krueger LJ: MicroRNA let-7a down-regulates MYC and reverts MYC-induced growth in Burkitt lymphoma cells. Cancer Res. 2007, 67: 9762-9770. 10.1158/0008-5472.CAN-07-2462.

PubMedGoogle Scholar

Johnson SM, Grosshans H, Shingara J, Byrom M, Jarvis R, Cheng A, Labourier E, Reinert KL, Brown D, Slack FJ: RAS is regulated by the let-7 microRNA family. Cell. 2005, 120: 635-647. 10.1016/j.cell.2005.01.014.

PubMedGoogle Scholar

Lee YS, Dutta A: The tumor suppressor microRNA let-7 represses the HMGA2 oncogene. Genes Dev. 2007, 21: 1025-1030. 10.1101/gad.1540407.

PubMedCentralPubMedGoogle Scholar

Ugalde AP, Ramsay AJ, de la Rosa J, Varela I, Marino G, Cadinanos J, Lu J, Freije JM, Lopez-Otin C: Aging and chronic DNA damage response activate a regulatory pathway involving miR-29 and p53. EMBO J. 2011, 30: 2219-2232. 10.1038/emboj.2011.124.

PubMedCentralPubMedGoogle Scholar

Zhang Y, Wu L, Wang Y, Zhang M, Li L, Zhu D, Li X, Gu H, Zhang CY, Zen K: Protective role of estrogen-induced miRNA-29 expression in carbon tetrachloride-induced mouse liver injury. J Biol Chem. 2012, 287: 14851-14862. 10.1074/jbc.M111.314922.

PubMedCentralPubMedGoogle Scholar

Garzon R, Heaphy CE, Havelange V, Fabbri M, Volinia S, Tsao T, Zanesi N, Kornblau SM, Marcucci G, Calin GA, Andreeff M, Croce CM: MicroRNA 29b functions in acute myeloid leukemia. Blood. 2009, 114: 5331-5341. 10.1182/blood-2009-03-211938.

PubMedCentralPubMedGoogle Scholar

Garzon R, Liu S, Fabbri M, Liu Z, Heaphy CE, Callegari E, Schwind S, Pang J, Yu J, Muthusamy N, Havelange V, Volinia S, Blum W, Rush LJ, Perrotti D, Andreeff M, Bloomfield CD, Byrd JC, Chan K, Wu LC, Croce CM, Marcucci G: MicroRNA-29b induces global DNA hypomethylation and tumor suppressor gene reexpression in acute myeloid leukemia by targeting directly DNMT3A and 3B and indirectly DNMT1. Blood. 2009, 113: 6411-6418. 10.1182/blood-2008-07-170589.

PubMedCentralPubMedGoogle Scholar

Kapinas K, Kessler CB, Delany AM: miR-29 suppression of osteonectin in osteoblasts: regulation during differentiation and by canonical Wnt signaling. J Cell Biochem. 2009, 108: 216-224. 10.1002/jcb.22243.

PubMedCentralPubMedGoogle Scholar

Mott JL, Kobayashi S, Bronk SF, Gores GJ: mir-29 regulates Mcl-1 protein expression and apoptosis. Oncogene. 2007, 26: 6133-6140. 10.1038/sj.onc.1210436.

PubMedCentralPubMedGoogle Scholar

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

PubMedGoogle Scholar

Filkowski JN, Ilnytskyy Y, Tamminga J, Koturbash I, Golubov A, Bagnyukova T, Pogribny IP, Kovalchuk O: Hypomethylation and genome instability in the germline of exposed parents and their progeny is associated with altered miRNA expression. Carcinogenesis. 2010, 31: 1110-1115. 10.1093/carcin/bgp300.

PubMedGoogle Scholar

Luna C, Li G, Qiu J, Epstein DL, Gonzalez P: Cross-talk between miR-29 and transforming growth factor-bs in trabecular meshwork cells. Invest Ophthalmol Vis Sci. 2011, 52: 3567-3572. 10.1167/iovs.10-6448.

PubMedCentralPubMedGoogle Scholar

Raver-Shapira N, Marciano E, Meiri E, Spector Y, Rosenfeld N, Moskovits N, Bentwich Z, Oren M: Transcriptional activation of miR-34a contributes to p53-mediated apoptosis. Mol Cell. 2007, 26: 731-743. 10.1016/j.molcel.2007.05.017.

PubMedGoogle Scholar

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: A microRNA component of the p53 tumour suppressor network. Nature. 2007, 447: 1130-1134. 10.1038/nature05939.

PubMedCentralPubMedGoogle Scholar

Bommer GT, Gerin I, Feng Y, Kaczorowski AJ, Kuick R, Love RE, Zhai Y, Giordano TJ, Qin ZS, Moore BB, MacDougald OA, Cho KR, Fearon ER: p53-mediated activation of miRNA34 candidate tumor-suppressor genes. Curr Biol. 2007, 17: 1298-1307. 10.1016/j.cub.2007.06.068.

PubMedGoogle Scholar

Fujita Y, Kojima K, Hamada N, Ohhashi R, Akao Y, Nozawa Y, Deguchi T, Ito M: Effects of miR-34a on cell growth and chemoresistance in prostate cancer PC3 cells. Biochem Biophys Res Commun. 2008, 377: 114-119. 10.1016/j.bbrc.2008.09.086.

PubMedGoogle Scholar

Leucci E, Cocco M, Onnis A, De Falco G, van Cleef P, Bellan C, van Rijk A, Nyagol J, Byakika B, Lazzi S, Tosi P, van Krieken H, Leoncini L: MYC translocation-negative classical Burkitt lymphoma cases: an alternative pathogenetic mechanism involving miRNA deregulation. J Pathol. 2008, 216: 440-450. 10.1002/path.2410.

PubMedGoogle Scholar

Wei JS, Song YK, Durinck S, Chen QR, Cheuk AT, Tsang P, Zhang Q, Thiele CJ, Slack A, Shohet J, Khan J: The MYCN oncogene is a direct target of miR-34a. Oncogene. 2008, 27: 5204-5213. 10.1038/onc.2008.154.

PubMedCentralPubMedGoogle Scholar

Yamakuchi M, Ferlito M, Lowenstein CJ: miR-34a repression of SIRT1 regulates apoptosis. Proc Natl Acad Sci U S A. 2008, 105: 13421-13426. 10.1073/pnas.0801613105.

PubMedCentralPubMedGoogle Scholar

Lodygin D, Tarasov V, Epanchintsev A, Berking C, Knyazeva T, Korner H, Knyazev P, Diebold J, Hermeking H: Inactivation of miR-34a by aberrant CpG methylation in multiple types of cancer. Cell Cycle. 2008, 7: 2591-2600. 10.4161/cc.7.16.6533.

PubMedGoogle Scholar

Siegel R, Naishadham D, Jemal A: Cancer statistics, 2012. CA Cancer J Clin. 2012, 62: 10-29. 10.3322/caac.20138.

PubMedGoogle Scholar

Vanharanta S, Massague J: Origins of metastatic traits. Cancer Cell. 2013, 24: 410-421. 10.1016/j.ccr.2013.09.007.

PubMedCentralPubMedGoogle Scholar

Taylor MA, Parvani JG, Schiemann WP: The pathophysiology of epithelial-mesenchymal transition induced by transforming growth factor-b in normal and malignant mammary epithelial cells. J Mammary Gland Biol Neoplasia. 2010, 15: 169-190. 10.1007/s10911-010-9181-1.

PubMedCentralPubMedGoogle Scholar

Martello G, Rosato A, Ferrari F, Manfrin A, Cordenonsi M, Dupont S, Enzo E, Guzzardo V, Rondina M, Spruce T, Parenti AR, Daidone MG, Bicciato S, Piccolo S: A MicroRNA targeting dicer for metastasis control. Cell. 2010, 141: 1195-1207. 10.1016/j.cell.2010.05.017.

PubMedGoogle Scholar

Hurst DR, Edmonds MD, Welch DR: Metastamir: the field of metastasis-regulatory microRNA is spreading. Cancer Res. 2009, 69: 7495-7498. 10.1158/0008-5472.CAN-09-2111.

PubMedCentralPubMedGoogle Scholar

White NM, Fatoohi E, Metias M, Jung K, Stephan C, Yousef GM: Metastamirs: a stepping stone towards improved cancer management. Nat Rev Clin Oncol. 2011, 8: 75-84. 10.1038/nrclinonc.2010.173.

PubMedGoogle Scholar

Korpal M, Lee ES, Hu G, Kang Y: The miR-200 family inhibits epithelial-mesenchymal transition and cancer cell migration by direct targeting of E-cadherin transcriptional repressors ZEB1 and ZEB2. J Biol Chem. 2008, 283: 14910-14914. 10.1074/jbc.C800074200.

PubMedCentralPubMedGoogle Scholar

Park SM, Gaur AB, Lengyel E, Peter ME: The miR-200 family determines the epithelial phenotype of cancer cells by targeting the E-cadherin repressors ZEB1 and ZEB2. Genes Dev. 2008, 22: 894-907. 10.1101/gad.1640608.

PubMedCentralPubMedGoogle Scholar

Gregory PA, Bert AG, Paterson EL, Barry SC, Tsykin A, Farshid G, Vadas MA, Khew-Goodall Y, Goodall GJ: The miR-200 family and miR-205 regulate epithelial to mesenchymal transition by targeting ZEB1 and SIP1. Nat Cell Biol. 2008, 10: 593-601. 10.1038/ncb1722.

PubMedGoogle Scholar

Gibbons DL, Lin W, Creighton CJ, Rizvi ZH, Gregory PA, Goodall GJ, Thilaganathan N, Du L, Zhang Y, Pertsemlidis A, Kurie JM: Contextual extracellular cues promote tumor cell EMT and metastasis by regulating miR-200 family expression. Genes Dev. 2009, 23: 2140-2151. 10.1101/gad.1820209.

PubMedCentralPubMedGoogle Scholar

Korpal M, Ell BJ, Buffa FM, Ibrahim T, Blanco MA, Celia-Terrassa T, Mercatali L, Khan Z, Goodarzi H, Hua Y, Wei Y, Hu G, Garcia BA, Ragoussis J, Amadori D, Harris AL, Kang Y: Direct targeting of Sec23a by miR-200s influences cancer cell secretome and promotes metastatic colonization. Nat Med. 2011, 17: 1101-1108. 10.1038/nm.2401.

PubMedCentralPubMedGoogle Scholar

Ma L, Young J, Prabhala H, Pan E, Mestdagh P, Muth D, Teruya-Feldstein J, Reinhardt F, Onder TT, Valastyan S, Westermann F, Speleman F, Vandesompele J, Weinberg RA: miR-9, a MYC/MYCN-activated microRNA, regulates E-cadherin and cancer metastasis. Nat Cell Biol. 2010, 12: 247-256.

PubMedCentralPubMedGoogle Scholar

Chen D, Sun Y, Wei Y, Zhang P, Rezaeian AH, Teruya-Feldstein J, Gupta S, Liang H, Lin HK, Hung MC, Ma L: LIFR is a breast cancer metastasis suppressor upstream of the Hippo-YAP pathway and a prognostic marker. Nat Med. 2012, 18: 1511-1517. 10.1038/nm.2940.

PubMedCentralPubMedGoogle Scholar

Zheng L, Qi T, Yang D, Qi M, Li D, Xiang X, Huang K, Tong Q: microRNA-9 suppresses the proliferation, invasion and metastasis of gastric cancer cells through targeting cyclin D1 and Ets1. PLoS One. 2013, 8: e55719-10.1371/journal.pone.0055719.

PubMedCentralPubMedGoogle Scholar

Valastyan S, Reinhardt F, Benaich N, Calogrias D, Szasz AM, Wang ZC, Brock JE, Richardson AL, Weinberg RA: A pleiotropically acting microRNA, miR-31, inhibits breast cancer metastasis. Cell. 2009, 137: 1032-1046. 10.1016/j.cell.2009.03.047.

PubMedCentralPubMedGoogle Scholar

Valastyan S, Benaich N, Chang A, Reinhardt F, Weinberg RA: Concomitant suppression of three target genes can explain the impact of a microRNA on metastasis. Genes Dev. 2009, 23: 2592-2597. 10.1101/gad.1832709.

PubMedCentralPubMedGoogle Scholar

Sossey-Alaoui K, Downs-Kelly E, Das M, Izem L, Tubbs R, Plow EF: WAVE3, an actin remodeling protein, is regulated by the metastasis suppressor microRNA, miR-31, during the invasion-metastasis cascade. Int J Cancer. 2011, 129: 1331-1343. 10.1002/ijc.25793.

PubMedCentralPubMedGoogle Scholar

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

PubMedGoogle Scholar

Dykxhoorn DM, Wu Y, Xie H, Yu F, Lal A, Petrocca F, Martinvalet D, Song E, Lim B, Lieberman J: miR-200 enhances mouse breast cancer cell colonization to form distant metastases. PLoS One. 2009, 4: e7181-10.1371/journal.pone.0007181.

PubMedCentralPubMedGoogle Scholar

Ma L: Role of miR-10b in breast cancer metastasis. Breast Cancer Res. 2010, 12: 210-10.1186/bcr2720.

PubMedCentralPubMedGoogle Scholar

Tian Y, Luo A, Cai Y, Su Q, Ding F, Chen H, Liu Z: MicroRNA-10b promotes migration and invasion through KLF4 in human esophageal cancer cell lines. J Biol Chem. 2010, 285: 7986-7994. 10.1074/jbc.M109.062877.

PubMedCentralPubMedGoogle Scholar

Ma L, Reinhardt F, Pan E, Soutschek J, Bhat B, Marcusson EG, Teruya-Feldstein J, Bell GW, Weinberg RA: Therapeutic silencing of miR-10b inhibits metastasis in a mouse mammary tumor model. Nat Biotechnol. 2010, 28: 341-347. 10.1038/nbt.1618.

PubMedCentralPubMedGoogle Scholar

Seoudi AM, Lashine YA, Abdelaziz AI: MicroRNA-181a - a tale of discrepancies. Expert Rev Mol Med. 2012, 14: e5-

PubMedGoogle Scholar

Taylor MA, Sossey-Alaoui K, Thompson CL, Danielpour D, Schiemann WP: TGF-β upregulates miR-181a expression to promote breast cancer metastasis. J Clin Invest. 2013, 123: 150-163. 10.1172/JCI64946.

PubMedCentralPubMedGoogle Scholar

Wang Y, Yu Y, Tsuyada A, Ren X, Wu X, Stubblefield K, Rankin-Gee EK, Wang SE: Transforming growth factor-b regulates the sphere-initiating stem cell-like feature in breast cancer through miRNA-181 and ATM. Oncogene. 2011, 30: 1470-1480. 10.1038/onc.2010.531.

PubMedCentralPubMedGoogle Scholar

Parikh A, Lee C, Peronne J, Marchini S, Baccarini A, Kolev V, Romualdi C, Fruscio R, Shah H, Wang F, Mullokandov G, Fishman D, D'Incalci M, Rahaman J, Kalir T, Redline RW, Brown BD, Narla G, Di Feo A: microRNA-181a has a critical role in ovarian cancer progression through the regulation of the epithelial-mesenchymal transition. Nat Commun. 2014, 5: 2977-

PubMedCentralPubMedGoogle Scholar

Weiler J, Hunziker J, Hall J: Anti-miRNA oligonucleotides (AMOs): ammunition to target miRNAs implicated in human disease?. Gene Ther. 2006, 13: 496-502. 10.1038/sj.gt.3302654.

PubMedGoogle Scholar

Cummins LL, Owens SR, Risen LM, Lesnik EA, Freier SM, McGee D, Guinosso CJ, Cook PD: Characterization of fully 2′-modified oligoribonucleotide hetero- and homoduplex hybridization and nuclease sensitivity. Nucleic Acids Res. 1995, 23: 2019-2024. 10.1093/nar/23.11.2019.

PubMedCentralPubMedGoogle Scholar

Krutzfeldt J, Rajewsky N, Braich R, Rajeev KG, Tuschl T, Manoharan M, Stoffel M: Silencing of microRNAs in vivo with ‘antagomirs’. Nature. 2005, 438: 685-689. 10.1038/nature04303.

PubMedGoogle Scholar

Manoharan M: 2′-carbohydrate modifications in antisense oligonucleotide therapy: importance of conformation, configuration and conjugation. Biochim Biophys Acta. 1999, 1489: 117-130. 10.1016/S0167-4781(99)00138-4.

PubMedGoogle Scholar

Davis S, Lollo B, Freier S, Esau C: Improved targeting of miRNA with antisense oligonucleotides. Nucleic Acids Res. 2006, 34: 2294-2304. 10.1093/nar/gkl183.

PubMedCentralPubMedGoogle Scholar

Vester B, Wengel J: LNA (locked nucleic acid): high-affinity targeting of complementary RNA and DNA. Biochemistry. 2004, 43: 13233-13241. 10.1021/bi0485732.

PubMedGoogle Scholar

Elmen J, Lindow M, Schutz S, Lawrence M, Petri A, Obad S, Lindholm M, Hedtjarn M, Hansen HF, Berger U, Gullans S, Kearney P, Sarnow P, Straarup EM, Kauppinen S: LNA-mediated microRNA silencing in non-human primates. Nature. 2008, 452: 896-899. 10.1038/nature06783.

PubMedGoogle Scholar

Lanford RE, Hildebrandt-Eriksen ES, Petri A, Persson R, Lindow M, Munk ME, Kauppinen S, Orum H: Therapeutic silencing of microRNA-122 in primates with chronic hepatitis C virus infection. Science. 2010, 327: 198-201. 10.1126/science.1178178.

PubMedCentralPubMedGoogle Scholar

Ebert MS, Neilson JR, Sharp PA: MicroRNA sponges: competitive inhibitors of small RNAs in mammalian cells. Nat Methods. 2007, 4: 721-726. 10.1038/nmeth1079.

PubMedGoogle Scholar

Choi WY, Giraldez AJ, Schier AF: Target protectors reveal dampening and balancing of Nodal agonist and antagonist by miR-430. Science. 2007, 318: 271-274. 10.1126/science.1147535.

PubMedGoogle Scholar

Trang P, Wiggins JF, Daige CL, Cho C, Omotola M, Brown D, Weidhaas JB, Bader AG, Slack FJ: Systemic delivery of tumor suppressor microRNA mimics using a neutral lipid emulsion inhibits lung tumors in mice. Mol Ther. 2011, 19: 1116-1122. 10.1038/mt.2011.48.

PubMedCentralPubMedGoogle Scholar

Aagaard L, Rossi JJ: RNAi therapeutics: principles, prospects and challenges. Adv Drug Deliv Rev. 2007, 59: 75-86. 10.1016/j.addr.2007.03.005.

PubMedCentralPubMedGoogle Scholar

Michelfelder S, Trepel M: Adeno-associated viral vectors and their redirection to cell-type specific receptors. Adv Genet. 2009, 67: 29-60.

PubMedGoogle Scholar

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: Therapeutic microRNA delivery suppresses tumorigenesis in a murine liver cancer model. Cell. 2009, 137: 1005-1017. 10.1016/j.cell.2009.04.021.

PubMedCentralPubMedGoogle Scholar

Gumireddy K, Young DD, Xiong X, Hogenesch JB, Huang Q, Deiters A: Small-molecule inhibitors of microrna miR-21 function. Angew Chem Int Ed Engl. 2008, 47: 7482-7484. 10.1002/anie.200801555.

PubMedCentralPubMedGoogle Scholar

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: MicroRNA expression profiles classify human cancers. Nature. 2005, 435: 834-838. 10.1038/nature03702.

PubMedGoogle Scholar

Liu A, Tetzlaff MT, Vanbelle P, Elder D, Feldman M, Tobias JW, Sepulveda AR, Xu X: MicroRNA expression profiling outperforms mRNA expression profiling in formalin-fixed paraffin-embedded tissues. Int J Clin Exp Pathol. 2009, 2: 519-527.

PubMedCentralPubMedGoogle Scholar

Weiland M, Gao XH, Zhou L, Mi QS: Small RNAs have a large impact: circulating microRNAs as biomarkers for human diseases. RNA Biol. 2012, 9: 850-859. 10.4161/rna.20378.

PubMedGoogle Scholar

Published
2020-03-30
Section
Research Article