2012, Número 4
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Rev cubana med 2012; 51 (4)
MicroRNAs en el cáncer: de la investigación a la práctica clínica
Frontela NM
Idioma: Español
Referencias bibliográficas: 62
Paginas: 325-335
Archivo PDF: 139.25 Kb.
RESUMEN
Los microRNAs (miRNAS) son una clase de RNAs no codificantes que actúan como reguladores de la expresión génica. Las secuencias de muchos de ellos están conservadas entre organismos no relacionados, lo cual sugiere que estas moléculas participan en procesos biológicos esenciales. Frecuentemente, la expresión de los miRNAs está alterada en muchos tipos de cánceres humanos y resultan críticos en la carcinogénesis, ya que funcionan como genes supresores tumorales o como oncogenes. Estudios recientes han demostrado que los miRNAs están muy relacionados con la progresión del cáncer, que incluye el crecimiento del tumor, la diferenciación, la adhesión, la apoptosis, la invasión y la formación de metástasis. En esta revisión se presenta la investigación básica y traslacional que ha emergido en la última década, un período que puede ser considerado como el de la "revolución de los miRNAs" en la oncología molecular. En ella se incluyen las características de los miRNAs, su biogénesis y procesamiento, sus funciones y los mecanismos que alteran su expresión en cáncer. Los miRNAs han generado un gran interés por sus aplicaciones potenciales en medicina, por lo que, además, se refieren sus perspectivas futuras en el diagnóstico, pronóstico y terapia del cáncer.
REFERENCIAS (EN ESTE ARTÍCULO)
Ponting CP, Belgard TG. Transcribed dark matter: meaning or myth? Hum Mol Genet. 2010;19(R2):R162-68.
Birney E, Stamatoyannopoulos JA, Dutta A, Guigo R, Gingeras TR, Margulies EH et al. Identification and analysis of functional elements in 1 % of the human genome by the ENCODE pilot project. Nature. 2007;447(7146):799-816.
Costa FF. Non-coding RNAs. Meet thy masters. Bioessays. 2010;32(7):599-608.
Van Bakel H, Nislow C, Blencowe BJ, Hughes TR. Most "dark matter" transcripts are associated with known genes. PLoS Biol. 010;8(5):e1000371.
Khachane AN, Harrison PM. Mining mammalian transcript data for functional long non-coding RNAs. PLoS One. 2010;5(4):e10316.
Gibb EA, Brown CJ, Lam WL. The functional role of long non-coding RNA in human carcinomas. Molecular Cancer. 2011;10:38 [citado 20 Dic 2011]. Disponible en: http://www.molecular-cancer.com/content/10/1/38
Mercer TR, Dinger ME, Mattick JS. Long non-coding RNAs: insights into functions. Nat Rev Genet. 2009;10(3):155-9.
Ponting CP, Oliver PL, Reik W. Evolution and functions of long noncoding RNAs. Cell. 2009;136(4):629-41.
Esquela-Kerscher A, Snack FJ. Oncomirs-microRNAs with a role in cancer. Nat Rev Cancer. 2006;6(4):259-69.
Kim VN, Nam JW. Genomics of microRNA. Trends Genet. 2006;22:165-73.
Stanczyk J, Pedrioli DM, Brentano F, Sanchez-Pernaute O, Kolling C, Gay RE, et al. Altered expression of MicroRNA in synovial fibroblasts and synovial tissue in rheumatoid arthritis. Arthritis Rheum. 2008;58:1001-9.
Krek A, Grun D, Poy MN, Wolf R, Rosenberg L, Epstein EJ, et al. Combinatorial microRNA target predictions. Nat Genet. 2005;37:495-500.
Bartel DP. MicroRNAs: genomics, biogenesis, mechanism and function. Cell. 2004; 116:281-97.
Lee Y, Kim M, Han J, Yeom KH, Lee S, Baek SH, et al. MicroRNA genes are transcribed by RNA polymerase II. EMBO J. 2004;23:4051-60.
Gu TJ, Yi X, Zhao XW, Zhao Y, Yin JQ. Alu-directed transcriptional regulation of some novel miRNAs. BMC Genomics. 2009;10:563.
Cai X, Hagedorn CH, Cullen BR. Human microRNAs are processed from capped, polyadenylated transcripts that can also function as mRNAs. RNA. 2004;10:1957-66.
Han J, Lee Y, Yeom KH, Kim YK, Jin H, Kim VN. The Drosha-DGCR8 complex in primary microRNA processing. Genes Dev. 2004;18:3016-27.
Han J, Lee Y, Yeom KH, Nam JW, Heo I, Rhee JK. Molecular basis for the recognition of primary microRNAs by the Drosha-DGCR8 complex. Cell. 2006;125:887-901.
Tang G. siRNA and miRNA: an insight into RISCs. Trends Biochem Sci. 2005;30:106-14.
Budhu A, Ji J, Wang XW. The clinical potential of microRNAs. J Hemathol Oncol. 2010;3:37. [citado 23 Dic 2011]. Disponible en: http://www.jhoonline.org/content/3/1/37
Liu J, Zheng M, Tang Y, Liang X, Yang Q. MicroRNAs, an active and versatile group in cancers. Int J Oral Sci. 2011;3:165-75.
Garzon R, Fabbri M, Cimmino A, Calin GA, Croce CM. MicroRNA expression and function in cancer. Trends Mol Med. 2006;12:580-7.
Lee RC, Feinbaum RL, Ambros V. The C. elegans heterochronic gene lin-4 encodes small RNAs with antisense complementarity to lin-14. Cell. 1993;75:843-54.
Reinhart BJ, Slack FJ, Basson M, Pasquinelli AE, Bettinger JC, Rougvie AE, et al. The 21-nucleotide let-7 RNA regulates developmental timing in Caenorhabditis elegans. Nature. 2000;403:901-6.
Pasquinelli AE, Reinhart BJ, Slack F, Martindale MQ, Kuroda MI, Maller B, et al. Conservation of the sequence and temporal expression of let-7 heterochronic regulatory RNA. Nature. 2000;408:86-9.
Lagos-Quintana M, Rauhut R, Lendeckel W, Tuschl T. Identification of novel genes coding for small expressed RNAs. Science. 2001;294:853-8.
Lau NC, Lim LP, Weinstein EG, Bartel DP. An abundant class of tiny RNAs with probable regulatory roles in Caenorhabditis elegans. Science. 2001;294:858-62.
Lee RC, Ambros V. An extensive class of small RNAs in Caenorhabditis elegans. Science. 2001;294:862-4.
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 USA. 2005;102:13944-9.
Jiang X, Wang X. Cytochrome C-mediated apoptosis. Annu Rev Biochem. 2004;73:87-106.
Cory S, Huang DC, Adams JM. The Bcl-2 family: roles in cell survival and oncogenesis. Oncogene. 2003;22:8590-607.
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;120:635-47.
Welch C, Chen Y, Stallings RL. MicroRNA-34a functions as a potential tumor suppressor by inducing apoptosis in neuroblastoma cells. Oncogene. 2007;26:5017-22.
Tazawa H, Tsuchiya N, Izumiya M, Nakagama H. Tumor-suppressive miR-34a induces senescence-like growth arrest through modulation of the E2F pathway in human colon cancer cells. Proc Natl Acad Sci USA. 2007;104:15472-7.
Mendell JT. miRiad roles for the miR-17-92 cluster in development and disease. Cell. 2008;133:217-22.
Petrocca F, Visone R, Onelli MR, Shah MH, Nicoloso MS, de Martino I, et al. E2F1-regulated microRNAs impair TGFbeta-dependent cell-cycle arrest and apoptosis in gastric cancer. Cancer Cell. 2008;13:272-86.
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;65:9628-32.
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;435:828-33.
Woods K, Thomson JM, Hammond SM. Direct regulation of an oncogenic micro-RNA cluster by E2F transcription factors. J Biol Chem. 2007;282:2130-4.
Sylvestre Y, De Guire V, Querido E, Mukhopadhyay UK, Bourdeau V, Major F, et al. An E2F/miR-20a autoregulatory feedback loop. J Biol Chem. 2007;282:2135-43.
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;133:647-58.
Frankel LB, Christoffersen NR, Jacobsen A, Lindow M, Krogh A, Lund AH. Programmed Cell Death 4 (PDCD4) Is an Important Functional Target of the MicroRNA miR-21 in Breast Cancer Cells. J Biol Chem. 2008;283:1026-33.
Vigorito E, Perks KL, Abreu-Goodger C, Bunting S, Xiang Z, Kohlhaas S, et al. microRNA-155 Regulates the Generation of Immunoglobulin Class-Switched Plasma Cells. Immunity. 2007;27:847-59.
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. Adv Exp Med Biol. 2007;604:17-46.
Wu W, Sun M, Zou GM, Chen J. MicroRNA and cancer: Current status and prospective. Int J Cancer. 2007;120:953-60.
MacFarlane LA, Murphy PR. MicroRNA: Biogenesis, function and role in cancer. Current Genomics. 2010;7(11):537-61.
O'Donnell KA, Wentzel EA, Zeller KI, Dang CV, Mendell JT. c-Myc-regulated microRNAs modulate E2F1 expression. Nature. 2005;435:839-43.
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;353:1793-801.
Melo SA, Esteller M. A precursor microRNA in a cancer cell nucleus. Get me out of here! Cell Cycle. 2011; 6(10):922-5.
Hoshida Y, Villanueva A, Kobayashi M, Peix J, Chiang DY, Camargo A, et al. Gene Expression in Fixed Tissues and Outcome in Hepatocellular Carcinoma. N Engl J Med. 2008;19(359):1995-2004.
Park NJ, Zhou H, Elashoff D, Henson BS, Kastratovic DA, Abemayor E, et al. Salivary microRNA: discovery, characterization and clinical utility for oral cancer detection. Clin Cancer Res. 2009;15:5473-7.
Wang J, Chen J, Chang P, Leblanc A, Li D, Abbruzzesse JL, et al. MicroRNAs in plasma of pancreatic ductal adenocarcinoma patients as novel blood-based biomarkers of disease. Cancer Prev Res. 2009;2:807-13.
Lu J, Getz G, Miska EA. MicroRNA expression profiles classify human cancers. Nature. 2005;435:834-8.
Yanaihara N, Caplen N, Bowman E, Seike M, Kumamoto K, Yi M, et al. Unique microRNA molecular profiles in lung cancer diagnosis and prognosis. Cancer Cell. 2006;9:189-98.
Chung GE, Yoon JH, Myung SJ, Lee JH, Lee SH, Lee SM, et al. High expression of microRNA-15b predicts a low risk of tumor recurrence following curative resection of hepatocellular carcinoma. Oncol Rep. 2010;23:113-9.
Coulouarn C, Factor VM, Andersen JB, Durkin ME, Thorgeirsson SS. Loss of miR-122 expression in liver cancer correlates with suppression of the hepatic phenotype and gain of metastatic properties. Oncogene. 2009;28:3526-36.
Weizhu Z, Wenyi Q, Ulus A, Edward RS. Circulating microRNAs in breast cancer and healthy subjects. BMC Research Notes. 2009;2:89.
Huang YS, Dai Y, Yu XF, Bao SY, Yin YB, Tang M, et al. Microarray analysis of microRNA expression in hepatocellular carcinoma and non-tumorous tissues without viral hepatitis. J Gastroenterol Hepatol. 2008;23:87-94.
Chin LJ, Ratner E, Leng S. A SNP in a let-7 microRNA complementary site in the KRAS 30 untranslated region increases non-small cell lung cancer risk. Cancer Res. 2008;68:8535-40.
Soifer HS, Rossi JJ, Saetrom P. MicroRNAs in disease and potential therapeutic applications. Mol Ther. 2007;15:2070-9.
Palmero EI, de Campos SGP, Campos M. Mechanisms and role of microRNA deregulation in cancer onset and progression. Genetics Molecular Biology. 2011;(34)3:363-70.
Ebert MS, Neilson JR, Sharp PA. MicroRNA sponges: Competitive inhibitors of small RNAs in mammalian cells. Nat Methods. 2007;4:721-6.