MicroRNAs, câncer e radiação ionizante: em que ponto
                  estamos?

Marta, Gustavo Nader; Garicochea, Bernardo; Carvalho, André Lopes; Real, Juliana M.; Kowalski, Luiz Paulo

doi:10.1590/1806-9282.61.03.275

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Sumário

REVIEW ARTICLES • Rev. Assoc. Med. Bras. 61 (3) • May-Jun 2015 • https://doi.org/10.1590/1806-9282.61.03.275 copiar

MicroRNAs, câncer e radiação ionizante: em que ponto estamos?

Autoria SCIMAGO INSTITUTIONS RANKINGS

Resumo

O objetivo do presente estudo é descrever a biogênese do microRNA, suas relações na carcinogênese e a correlação do microRNA com a radiação ionizante (RI), com enfoque na radiorresponsividade. Observou-se que a biogênese do microRNA está bem estabelecida e envolve diversas clivagens enzimáticas que resultam na produção do microRNA maduro. Os microRNAs estão envolvidos na carcinogênese. Sua interação está relacionada às alterações genéticas e epigenéticas, associadas à ativação de proto- -oncogenes ou à inativação de genes supressores de tumor. Vários estudos demonstraram que os níveis de expressão de alguns microRNAs variam significativamente após a irradiação. Há evidências de que os microRNAs podem influenciar a resposta celular após a RI. Além disso, os microRNAs estão relacionados à modulação da expressão de vários alvos de pós-transcrição das vias de resposta aos danos no DNA e o do mecanismo de regulação de reparação de danos do DNA. Estudos futuros podem elucidar uma possível utilização clínica dos microRNAs como uma nova classe de agentes radiossensíveis.

Palavras-chave:
microRNAs; neoplasias; radioterapia de alta energia

Cell type	Increase	Decrease
Central nervous system
Glioma³¹31 Rhodes LV, Nitschke AM, Segar HC, Martin EC, Driver JL, Elliott S, et al. The histone deacetylase inhibitor trichostatin A alters microRNA expression profiles in apoptosis-resistant breast cancer cells. Oncol Rep. 2012; 27(1):10-6. ^, ³²32 Wang Y, Medvid R, Melton C, Jaenisch R, Blelloch R. DGCR8 is essential for microRNA biogenesis and silencing of embryonic stem cell self-renewal. Nat Genet. 2007; 39(3):380-5. ^, ³³33 Kumar MS, Pester RE, Chen CY, Lane K, Chin C, Lu J, et al. Dicer1 functions as a haploinsufficient tumor suppressor. Genes Dev. 2009; 23(23):2700-4.	let-7a; let-7b; let-7c; let-7d; let-7e; let-7f; let-7g; let-7i; miR-15a;	miR-107; miR-181a; miR-521
	miR-16; miR-17-3p; miR-17-5p; miR-19a; miR-19b; miR-22;
	miR-21; miR-142-3p; miR-142-5p; miR-143; miR-155; miR-191;
	miR-379; miR-601
Mouse hippocampal cells and brain tissue³⁴34 Karube Y, Tanaka H, Osada H, Tomida S, Tatematsu Y, Yanagisawa K, et al. Reduced expression of Dicer associated with poor prognosis in lung cancer patients. Cancer Sci. 2005; 96(2):111-5.	miR-21	–
Head and neck
Thyroid³⁵35 Grelier G, Voirin N, Ay AS, Cox DG, Chabaud S, Treilleux I, et al. Prognostic value of Dicer expression in human breast cancers and association with the mesenchymal phenotype. Br J Cancer. 2009; 101(4):673-83. ^, ³⁶36 Lin RJ, Lin YC, Chen J, Kuo HH, Chen YY, Diccianni MB, et al. MicroRNA signature and expression of Dicer and Drosha can predict prognosis and delineate risk groups in neuroblastoma. Cancer Res. 2010; 70(20):7841-50.	let-7c; let-7d; let-7g; miR-17-3p; miR-17-5p; miR-27b;	let-7f; let-7g; miR-10a; miR-106a; miR-152
	miR-34a; miR-34b; miR-188-5p; miR-365
Thorax
Lung cancer and normal epithelial cell line³⁷37 Guo X, Liao Q, Chen P, Li X, Xiong W, Ma J, et al. The microRNA-processing enzymes: Drosha and Dicer can predict prognosis of nasopharyngeal carcinoma. J Cancer Res Clin Oncol. 2012; 138(1):49-56. ^, ³⁸38 Martello G, Rosato A, Ferrari F, Manfrin A, Cordenonsi M, Dupont S, et al. A MicroRNA targeting dicer for metastasis control. Cell. 2010; 141(7):1195-207. ^, ³⁹39 Piovan C, Palmieri D, Di Leva G, Braccioli L, Casalini P, Nuovo G, et al. Oncosuppressive role of p53-induced miR-205 in triple negative breast cancer. Mol Oncol. 2012; 6(4):458-72.	miR-15a; miR-16; miR-17-5p; miR-19a; miR-19b; miR-20b;	let-7a; let-7b; let-7c; let-7d; let-7e; let-7f;
	miR-22; miR-24; miR-27a; miR-27b; miR-30a-5p; miR-99a;	let-7i; miR-26b; miR-125a; miR-155;
	miR-106a; miR-148a; miR-221; miR-365; miR-126; let-7a;	miR 130a, miR-106b, miR-19b, miR-22,
	miR-495; miR-451; miR-128b	iR-15b, miR-17-5p; miR-21
Genitourinary
Prostate⁴⁰40 Mott JL, Kurita S, Cazanave SC, Bronk SF, Werneburg NW, Fernandez-Zapico ME. Transcriptional suppression of mir-29b-1/mir-29a promoter by c-Myc, hedgehog, and NF-kappaB. J Cell Biochem. 2010; 110(5):1155-64. ^, ⁴¹41 Burk U, Schubert J, Wellner U, Schmalhofer O, Vincan E, Spaderna S, et al. A reciprocal repression between ZEB1 and members of the miR-200 family promotes EMT and invasion in cancer cells. EMBO Rep. 2008; 9(6):582-9. ^, ⁴²42 Engels BM, Hutvagner G. Principles and effects of microRNA-mediated post-transcriptional gene regulation. Oncogene. 2006; 25(46):6163-9.	miR-191; miR-379; miR-29b 7; miR-191; miR-22; miR-200c;	miR-100; miR-107; miR-133b; miR-143;
	miR-191; miR-379; miR-29b 7; miR-191; miR-22; miR-200c;	miR-145; miR-196a; miR-521; miR-106b;
	miR-141; miR-24 ; miR-30a-5p; miR-9-1	miR-199a
Gastrointestinal
Rectum⁴³43 Deng S, Calin GA, Croce CM, Coukos G, Zhang L. Mechanisms of microRNA deregulation in human cancer. Cell Cycle. 2008; 7(17):2643-6. ^, ⁴⁴44 Bussing I, Slack FJ, Grosshans H. Let-7 microRNAs in development, stem cells and cancer. Trends Mol Med. 2008; 14(9):400-9.	miR-1183; miR-483-5p; miR-622; miR-125a-3p; miR-1224-5p;	miR-1274b; miR-720
	miR-188-5p; miR-1471; miR-671-5p; miR-1909; miR-630;
	miR-765; miR125b; miR137
Hematology
Non-Hodgkin lymphoma⁴⁵45 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):635-47.	miR-1913; miR-Plus-F1147; miR-148b; miR-589; miR-106b;	miR-29a; miR-335; miR-193b; miR-21;
	miR-Plus-G1246-3p; miR-19b; miR-1280; miR-BHRF1-1;	miR-340; miR-33a; let-7e; miR-Plus-E1098;
	miR-20a	miR-483-3p; miR-200b
Breast
Breast⁴⁶46 Dent P, Yacoub A, Fisher PB, Hagan MP, Grant S. MAPK pathways in radiation responses. Oncogene. 2003; 22(37):5885-96.	–	miR-302a; miR-302b; miR-302c;
	–	miR-302d; miR-302e
Other
Normal human fibroblasts⁴⁷47 Simone NL, Soule BP, Ly D, Saleh AD, Savage JE, Degraff W, et al. Ionizing radiation-induced oxidative stress alters miRNA expression. PLoS One. 2009; 4(7):e6377.	let-7d; let-7e; let-7f; let-7g; let-7i; miR-15a; miR-17-3p; miR-17-5p;	let-7a; let-7b; let-7d; miR-24; miR-155;
	miR-19b; miR-21; miR-26b; miR-142-3p; miR-142-5p; miR-143;	miR-222
	miR-145; miR-155; miR-663
Human 3-D airway model tissues⁴⁸48 Tarasov V, Jung P, Verdoodt B, Lodygin D, Epanchintsev A, Menssen A, et al. 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. 2007; 6(13):1586-93.	–	let-7a; let-7b; let-7c; let-7d; let-7e;
	–	let-7f; let-7g; let-7i
Lymphocytes⁴⁹49 Koturbash I, Zemp F, Kolb B, Kovalchuk O. Sex-specific radiation-induced microRNAome responses in the hippocampus, cerebellum and frontal cortex in a mouse model. Mutat Res. 2011; 722(2):114-8.	miR-16; miR-34a; miR-34b; miR-145; miR-188-5p; miR-221;	let-7e; miR-10a; miR-17; miR-19b; miR-99a;
	miR-601; miR-663	miR-100; miR-152;miR-181a; miR-196a
Blood⁵⁰50 Dickey JS, Zemp FJ, Martin OA, Kovalchuk O. The role of miRNA in the direct and indirect effects of ionizing radiation. Radiat Environ Biophys. 2011; 50(4):491-9.	let-7f; miR-16; miR-17-3p; miR-17-5p; miR-19a; miR-20a;	miR-143
	miR-20b; miR-21; miR-24; miR-27a; miR-29a; miR-29c;
	miR-106a; miR-126; miR-142-5p; miR-145; miR-148a;
	miR-222
Endothelial cell⁵¹51 Kraemer A, Anastasov N, Angermeier M, Winkler K, Atkinson MJ, Moertl S. MicroRNA-mediated processes are essential for the cellular radiation response. Radiat Res. 2011; 176(5):575-86.	let-7g; miR-16; miR-20a; miR-21; miR-29c	miR-125a
Human umbilical vein endothelial cells⁵²52 Surova O, Akbar NS, Zhivotovsky B. Knock-down of core proteins regulating microRNA biogenesis has no effect on sensitivity of lung cancer cells to ionizing radiation. PLoS One. 2012; 7(3):e33134.	miR-17-5p; miR-19a; miR-19b; miR-20a; miR-21; miR-27b;	–
	miR-29a; miR-29c; miR-126; miR-221; miR-222

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