DİLEK AŞCI ÇELİK, Pınar Aslan KO?AR, NURTEN ÖZÇELİK

MikroRNA’lar ve kanser ile ilişkisi

MikroRNAlar (miRNAlar), endojen küçük RNAlar?n bir s?n?f?n? olu?turan, protein kodlamayan, yakla??k20-23 nükleotid uzunlu?unda RNA molekülleridir. Bu moleküllerin özellikle hücre tipinin belirlenmesi vehücre farkl?la?mas? olmak üzere pek çok fizyolojik olaylarda ve patolojik durumlarda önemli düzenleyiciroller ald??? gösterilmi?tir. Ayr?ca kanserde hem onkojenik hem de tümör bask?lay?c? rol oynad?klar? aç??aç?km??t?r. Pek çok kanserde baz? miRNAlar?n onkogen, baz?lar?n?n ise tümör bask?lay?c? gen gibi i?levgörmesi, tümör ilerlemesi, metastaz? ve invazyonunda miRNAlar?n düzenleyici oldu?unu göstermektedir.miRNAlar?n karsinogenezde etkili olabileceklerinin anla??lmas?yla birlikte, farkl? kanser türlerinde spesifikhücre tiplerinde miRNAlar?n ekspresyon seviyelerindeki de?i?imler incelenmi?, miRNAlar?n normal vepatolojik dokular aras?nda farkl?l?k gösterdi?i belirlenmi?tir. Gen ekspresyonunu düzenledi?i gösterilenmiRNAlar?n kanser hücrelerindeki seviyelerinin normal hücrelerle kar??la?t?r?lmas? kanserin tan?, takip vetedavisinde önem kazanm??t?r. Son y?llarda i?levlerinin ve kanserdeki rollerinin anla??lmaya ba?lanmas? ilemiRNAlar kanserin moleküler patolojisinin anla??lmas?nda ve moleküler hedefe yönelik tedavilergeli?tirilmesinde umut olmu?tur

Micro RNAs and their relation with cancer

MicroRNAs (miRNAs) are class of small non-coding endogen RNA molecules usually 20-23 nucleotides at length. They have shown to role in many physiological and pathological processes including cell characterization and differentiation. Additionally some miRNAs were identified as oncogenes while some others are tumor-suppressors in cancer. This data indicates their modulatory effects on tumor progression, invasion and metastasis. After the effects of miRNA’s on carcinogenesis were discovered, expression levels of miRNAs on different cancer and normal cell lines were evaluated and differences found between normal and pathological tissues. Comparisons of miRNA expression levels between cancer and normal cells have gained attention on diagnosis, prognosis ant treatment of cancer. With the increasing knowledge about miRNA functions and their roles in cancer, they became new hope for understanding molecular pathology of cancer and for developing molecular targeting treatment method.

PDF

___

1. Zhang L, Huang J, Yang N, Greshock J, Megraw MS, Giannakakis A,et al. MicroRNAs exhibit high frequency genomic alterations in human cancer. 2006;103:9136- 41.
2. Le Quesne J, Caldas C. Micro-RNAs and breast cancer. Moleculer Oncology. 2010;4:230-41.
3. Gregory RI, Chendrimada TP, Cooch N, Shiekhattar R. Human RISC couples microRNA biogenesis and posttranscriptional gene silencing (Reprinted from Cell, vol 123, pg 631-640, 2005). Cell 2007; 131: 63-73.
4. Jackson RJ, Standart N. How do microRNAs regulate gene expression? Sci STKE. 2007;1:367.
5. Ambros V. The functions of animal microRNAs. Nature. 2004; 431(7006):350-5.
6. Bartel DP. MicroRNAs: genomics, biogenesis, mechanism, and f unction (reprinted from Cell, vol 116, pg 281297, 2004). Cell 2007;131:1129.
7. Nicoloso MS, Spizzo R, Shimizu M, Rossi S, Calin GA. MicroRNAs-the micro steering wheel of tumour metastases. Nat Rev Cancer 2009;9(4):293-302.
8. Bohnsack MT, Czaplinski K, Gorlich D. Exportin 5 is a RanGTP-dependent dsRNA-binding protein that mediates nuclear export of pre-miRNAs. Rna-A Publication of the Rna Society.2004; 10:185-91.
9. Lund E, Guttinger S, Calado A, Dahlberg JE, Kutay U. Nuclear export of microRNA precursors. Science 2004; 303: 95-8.
10. Yi R, Qin Y, Macara IG, Cullen BR. Exportin-5 mediates the nuclear export of pre-microRNAs and short hairpin RNAs. Genes & Development 2003;17:3011-6.
11. Garzon R, Fabbri M, Cimmino A, Calin GA, Croce CM. MicroRNA expression and function in cancer.Trends Mol Med. 2006;12(12):580-7.
12. Grishok A, Pasquinelli AE, Conte D, Li N, Parrish S, Ha I et al. Genes and mechanisms related to RNA interference regulate expression of the small temporal RNAs that control C-elegans developmental timing. Cell 2001;106:23-34.
13. Hutvagner G, McLachlan J, Pasquinelli AE, Balint E, Tuschl T, Zamore PD. A cellular function for the RNAinterference enzyme Dicer in the maturation of the let- 7 small temporal RNA. Science 2001;293:834-8.
14. Lin SL, Chang D, Ying SY. Asymmetry of intronic pre-miRNA structures in functional RISC assembly. Gene 2005;356:32-8.
15. Ghildiyal M, Zamore PD. Small silencing RNAs: an expanding universe. Nature Reviews Genetics 2009;10:94-108.
16. Forman JJ, Coller HA. The code within the code: MicroRNAs target coding regions. Cell Cycle 2010;9(8)1533-41.
17. Meister G. miRNAs get an early start on translational silencing. Cell 2007; 131: 25-8.
18. Pillai RS, Bhattacharyya SN, Artus CG, Tabea Z, Cougot N, Basyuk E, et al. Inhibition of Translational Initiation by Let-7 MicroRNA in Human Cells. Science 2005; 309:1573-76.
19. Hendrickson DG, Hogan DJ, McCullough HL, Myers JW, Herschlag D, Ferrell JE, et al. Concordant Regulation of Translation and mRNA Abundance for Hundreds of Targets of a Human microRNA. Plos Biology 2009; 7 (11): e1000238
20. Calin GA, Croce CM. MicroRNA signatures in human cancers.Nat Rev Cancer. 2006; 6(11): 857-66.
21. Wiemer EAC. The role of microRNAs in cancer: No small matter. European Journal of Cancer. 2007;43 (10):1529-44.
22. O'Donnell KA, Wentzel EA, Zeller KI, Dang CV, Mendell JT. c-Myc-regulated microRNAs modulate E2F1 expression. Nature 2005; 435: 839-43.
23. Hayashita Y, Osada H, Tatematsu Y, Yamada H, Yanagisowa 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: 962832
24. Meng F, Henson RH, Wehbe-Janek H. MicroRNA-21 regulates expression of the PTEN tumor suppressor gene in human hepatocellular cancer. Gastroenterology 2007;133:64758.
25. Volinia S, Calin G, Liu CG, Ambs S, Cimmino A, Petrocca F, et al. A microRNA expression signature in human solid tumors defines cancer targets. Proc. Natl. Acad. Sci. USA 2006;103:225761.
26. 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. New Engl J Med 2005;353(17):1793-801.
27. 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 USA 2004;101(9):2999-3004.
28. Lin PY ,Yu SL, Yang PC. MicroRNA in lung cancer. Brýtýsh Journal of Cancer 2010; 103:114448.
29. Iorio MV, Ferracin M, Liu C, Veronese A, Spizzo R, Sabbioni S, et al. MicroRNA gene expression deregulation in human breast cancer.Cancer Research 2005; 65:7065-70.
30. Slaby O, Svoboda M, Fabian P, Smerdova T, Knoflickova D, Bednarikova M, et al. Altered expression of miR-21, miR-31, miR-143 and miR-145 is related to clinicopathologic features of colorectal cancer. Oncology 2008;72:397-402.
31. 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. Nuc Nucleic Acids Res 2005; 33:1290-7.
32. Tanno B, Cesi V, Vitali R, Sesti F, Giuffrida ML, Mancini C et al. Silencing of endogenous IGFBP-5 by micro RNA interference affects proliferation, apoptosis and differentiation of neuroblastoma cells. Cell Death and Differentiation 2005;12:213-23.
33. Sevignani C, Calin GA, Siracusa LD, Croce CM. Mammalian microRNAs: a small world for fine-tuning gene expression. Mamm Genome 2006;17(3):189-202.
34. Zhou YM, Chen LJ, Barlogie B, Stephens O, Wu XS, Williams DR, et al. High-risk myeloma is associated with global elevation of miRNAs and overexpression of EIF2C2/AGO2. Proceedings of the National Academy of Sciences of the United States of America 2010;107:7904-9.
35. Kim YK, Yeo J, Ha M, Kim B, Kim VN. Cell adhesiondependent control of microRNA decay. Molecular Cell 2011;43:100514
36. 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 SA 2002; 99(24):15524-9.
37. 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):13944-9.
38. Michael MZ, OConnor SM, van Holst Pellekaan NG, Young GP, James RJ. Reduced accumulation of specific microRNAs in colorectal neoplasia. Mol Cancer Res 2003;1:88291
39. 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;39:1679.
40.Chan JA, Krichevsky AM, Kosik KS. MicroRNA-21 is an antiapoptotic factor in human glioblastoma cells. Cancer Res 2005;65:602933.
41.He H, Jazdzewski K, Li W, Liyanorachchi S, Nagy R, Volinia S, et al. The role of microRNA genes in papillary thyroid carcinoma. Proc Natl Acad Sci USA 2005;102:1907580.
42.Sevli S, Uzumcu A, Solak M, Ittman M, Ozen M. The function microRNAs, small potent molecules in human prostate cancer. Prostate Cancer P D 2010;13:208-17.
43.Lamy P, Andersen CL, Dyrskjøt L, Tørring N, Ørntoft T, Wiuf C. Are microRNAs located in genomic regions associated with cancer? Br J Cancer 2006; 95 (10): 1415-8.
44. Takamizawa J, Konishi H, Yanagisawa K, Tomida S, Osada H, Endoh H, et al. Reduced expression of the let-7 microRNAs in human lung cancers in association with shortened postoperative survival. Cancer Res 2004;64(11):3753-6.
45.Johnson SM, Grosshans H, Shingara J, Byrom M, Aþcý
Jarvis R, Cheng A, et al. RAS is regulated by the let- 7 MicroRNA family. Cell 2005; 120: 635-47.
46. Yu F, Yao H, Zhu P, Zhang X, Pan Q, Gong C, et al. let-7 regulates self renewal and tumorigenicity of breast cancer cells. Cell 2007; 131: 1109-23.
47. Lars D, Marie S and Jesper B. Genomic profiling of microRNAs in bladder cancer: miR-129 is associated with poor outcome and promotes cell death in vitro. Cancer Res.2009;69 4851-60.
48.James W F, Saiful M, Helen C O, Freddie C H.Distinct microRNA alterations characterize high and low grade cancer.Cancer res. 2009;69:8472-81.
49. Chen X, Guo X, Zhang H, Xiang Y, Chen J, Yin Y,et al. Role of miR-143 targeting KRAS in colorectal tumorigenesis.Oncogene.2009;28(10):1385-92.
50. Akao Y, Nakagawa Y, Hirata I, Iio A, Itoh T, Kojima K, et al. Role of anti-oncomirs miR-143 and -145 in human colorectal tumors. Cancer Gene Ther. 2010;17(6):398-408.
51. Saetrom P, Biesinger J, Li S M, Smith D, Thomas L F, Majzoub K,et al. A risk variant in an miR-125b binding site in BMPR1B is associated with breast cancer pathogenesis. Cancer Res. 2009; 69(18): 7459- 65.
52. Gefen N, Binder V, Zaliova M, Linka Y, Morrow M, Novosel A, et al. Hsa-mir 125b-2 is highly expressed in childhood ETV6/RUNX1 (TEL/AML1) leukemias and confers survival advantage to growth inhibitory signals independent of p53. Leukemia.2010; 24(1): 89-96.
53.Jiang JM, Lee EJ, Gusev Y, Schmittgen TD. Real-time expression profiling of microRNA precursors in human cancer cell lines. Nucleic Acids Res 2005; 33:53945403.