#PAGE_PARAMS# #ADS_HEAD_SCRIPTS# #MICRODATA#

Molecular Aspects of Thyroid Tumors with Emphasis on MicroRNA and Their Clinical Implications


Authors: M. Ludvíková 1,2;  I. Kholová 3;  D. Kalfeřt 4
Authors‘ workplace: Ústav biologie, LF UK v Plzni 1;  Ústav patologie, 1. LF UK a VFN v Praze 2;  Pathology, Fimlab Laboratories and Faculty of Medicine and Life Science, Tampere University Hospital, Tampere, Finland 3;  Klinika otorinolaryngologie a chirurgie hlavy a krku 1. LF UK a FN Motol, Praha 4
Published in: Klin Onkol 2017; 30(3): 167-174
Category: Review
doi: https://doi.org/10.14735/amko2017167

Overview

Background:
Central to neoplastic transformation and tumor progression is alteration of the signaling pathways that control cell proliferation and apoptosis. The key mechanisms for this neoplastic process are genetic changes (mutations of cancer-related genes) and recently identified epigenetic changes that involve DNA methylation, chromatin remodeling (which has a profound effect on the control of gene expression), and noncoding, regulatory RNA (notably, microRNA – miRNA). MiRNAs control expression of their target gene post-transcriptionally. These molecular factors have potential as diagnostic, prognostic, and predictive molecular markers. Epithelial tumors of the thyroid gland are a histogenetically, morphologically, and pathobiologically heterogeneous group of neoplasms and require new, molecular approaches in clinical practice.

Aim:
This review aims to present contemporary scientific knowledge of this molecular (genetic and epigenetic) field of sporadic thyroid tumors of follicular cell origin and their potential clinical implications. The fundamental mutations (BRAFV600E, RET/PTC, RAS, and PAX8-PPARG) in selected tumor types are described comprehensively. Special attention is paid to miRNAs, including their biogenesis, function, and expression profiles in the most common thyroid tumors – follicular adenoma, follicular carcinoma, and papillary carcinoma.

Conclusion:
Thyroid cancer medicine has recently entered a new, molecular era. Comprehensive knowledge of all molecular aspects may improve diagnostics and management of thyroid neoplasms through the introduction of novel, progressive treatment strategies for this cancer. Further research on signaling pathway-related targets, standardization of methods, and evaluation of results are required.

Key words:
thyroid tumors – cancerogenesis – genetics – epigenetics – microRNA

The authors declare they have no potential conflicts of interest concerning drugs, products, or services used in the study.

The Editorial Board declares that the manuscript met the ICMJE recommendation for biomedical papers.

Submitted:
19. 10. 2016

Accepted:
2. 11. 2016


Sources

1. Hedinger C, Williams ED, Sobin L. Histological Typing of Thyroid Tumours (WHO. World Health Organization. International Histological Classification of Tumours). 2nd ed. Berlin: Springer Science & Business Media 2013.

2. Xing M. Molecular pathogenesis and mechanisms of thyroid cancer. Nat Rev Cancer 2013; 13 (3): 184–199. doi: 10.1038/nrc3431.

3. Ludvíková M, Kholová I. Přehled dosavadních zkušeností s mezinárodní klasifikací tenkojehlové aspirační cytologie štítné žlázy Bethesda 2010. Cesk Patol 2014; 50 (3): 155–160.

4. Kholova I, Ludvikova M. Thyroid atypia of undetermined significance or follicular lesion of undetermined significance: an indispensable Bethesda 2010 diagnostic category or waste garbage? Acta Cytol 2014; 58 (4): 319–329.

5. Cibas ES, Ali SZ. The Bethesda System For Reporting Thyroid Cytopathology. Am J Clin Pathol 2009; 132 (5): 658–665. doi: 10.1309/AJCPPHLWMI3JV4LA.

6. Russo D, Damante G, Puxeddu E et al. Epigenetics of thyroid cancer and novel therapeutic targets. J Mol Endocrinol 2011; 46 (3): R73–R81. doi: 10.1530/JME-10-0150.

7. Catalano MG, Fortunati N, Boccuzzi G. Epigenetics modifications and therapeutic prospects in human thyroid cancer. Front Endocrinol (Lausanne) 2012; 3: 40.

8. Menon MP, Khan A. Micro-RNAs in thyroid neoplasms: molecular, diagnostic and therapeutic implications. J Clin Pathol 2009; 62 (11): 978–985. doi: 10.1136/jcp.2008.063909.

9. Xing M, Haugen BR, Schlumberger M. Progress in molecular-based management of differentiated thyroid cancer. Lancet 2013; 381 (9871): 1058–1069. doi: 10.1016/S0140-6736 (13) 60109-9.

10. Ludvíková M, Pešta M, Holubec L Jr et al. Nové aspekty patobiologie nádorů. Cesk Patol 2009; 45 (4): 94–99.

11. Faam B, Ghaffari MA, Ghadiri A et al. Epigenetic modifications in human thyroid cancer. Biomed Rep 2015; 3 (1): 3–8.

12. Tanaka TN, Alloju SK, Oh DK et al. Thyroid cancer: molecular pathogenesis, tyrosine kinase inhibitors, and other new therapies. Am J Hematol Oncol 2015; 11 (4): 5–9.

13. Papp S, Asa SL. When thyroid carcinoma goes bad: a morphological and molecular analysis. Head Neck Pathol 2015; 9 (1): 16–23. doi: 10.1007/s12105-015-0619-z.

14. Vu-Phan D, Koenig RJ. Genetics and epigenetics of sporadic thyroid cancer. Mol Cell Endocrinol 2014; 386 (1–2): 55–66. doi: 10.1016/j.mce.2013.07.030.

15. Boufraqech M, Patel D, Xiong Y et al. Diagnosis of thyroid cancer: state of art. Expert Opin Med Diagn 2013; 7 (4): 331–342. doi: 10.1517/17530059.2013.800481.

16. Gilfillan CP. Review of the genetics of thyroid tumours: diagnostic and prognostic implications. ANZ J Surg 2010; 80 (1–2): 33–40. doi: 10.1111/j.1445-2197.2009.05173.x.

17. Máximo V, Botelho T, Capela J et al. Somatic and germline mutation in GRIM-19, a dual function gene involved in mitochondrial metabolism and cell death, is linked to mitochondrion-rich (Hurthle cell) tumours of the thyroid. Br J Cancer 2005; 92 (10): 1892–1898.

18. Máximo V, Rios E, Sobrinho-Simoes M. Oncocytic lesions of the thyroid, kidney, salivary glands, adrenal cortex, and parathyroid glands. Int J Surg Pathol 2014; 22 (1): 33–36. doi: 10.1177/1066896913517938.

19. White MG, Nagar S, Aschebrook-Kilfoy B et al. Epigenetic Alterations and Canonical Pathway Disruption in Papillary Thyroid Cancer: A Genome-wide Methylation Analysis. Ann Surg Oncol 2016; 23 (7): 2302–2309. doi: 10.1245/s10434-016-5185-4.

20. Zhang R, Hardin H, Chen J et al. Non-Coding RNAs in Thyroid Cancer. Endocr Pathol 2016; 27 (1): 12–20. doi: 10.1007/s12022-016-9417-8.

21. 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.

22. Fire A, Xu S, Montgomery MK et al. Potent and specific genetic interference by double-stranded RNA in Caenorhabditis elegans. Nature 1998; 391 (6669): 806–811.

23. Tuschl T, Zamore PD, Lehmann R et al. Targeted mRNA degradation by double-stranded RNA in vitro. Genes Dev 1999; 13 (24): 3191–3197.

24. Zhou X, Yang PC. MicroRNA: a small molecule with a big biological impact. Microrna 2012; 1 (1): 1.

25. Ross JS, Carlson JA, Brock G. miRNA: the new gene silencer. Am J Clin Pathol 2007; 128 (5): 830–836.

26. Cammaerts S, Strazisar M, De Rijk P et al. Genetic variants in microRNA genes: impact on microRNA expression, function, and disease. Front Genet 2015; 6: 186. doi: 10.3389/fgene.2015.00186.

27. Rodrigues RF, Roque L, Rosa-Santos J et al. Chromosomal imbalances associated with anaplastic transformation of follicular thyroid carcinomas. Br J Cancer 2004; 90 (2): 492–496.

28. Kalfert D, Pesta M, Kulda V et al. MicroRNA profile in site-specific head and neck squamous cell cancer. Anticancer Res 2015; 35 (4): 2455–2463.

29. Vinklárek J, Novák J, Bienertová-Vašků J et al. Role mikroRNA v patofyziologii neuroblastomu a možnosti jejich využití pro diagnostiku, odhad prognózy a terapii. Klin Onkol 2014; 27 (5): 331–339. doi: 10.14735/ amko2014331.

30. Novák J, Souček M. MikroRNA a vnitřní lékařství: od patofyziologie k novým diagnostickým a terapeutickým postupům. Vnitr Lek 2016; 62 (6): 477–485.

31. Lu J, Getz G, Miska EA et al. MicroRNA expression profiles classify human cancers. Nature 2005; 435 (7043): 834–838.

32. Rossing M, Kaczkowski B, Futoma-Kazmierczak E et al. A simple procedure for routine RNA extraction and miRNA array analyses from a single thyroid in vivo fine needle aspirate. Scand J Clin Lab Invest 2010; 70 (8): 529–534. doi: 10.3109/00365513.2010.522250.

33. Agretti P, Ferrarini E, Rago T et al. MicroRNA expression profile helps to distinguish benign nodules from papillary thyroid carcinomas starting from cells of fine-needle aspiration. Eur J Endocrinol 2012; 167 (3): 393–400. doi: 10.1530/EJE-12-0400.

34. Chen YT, Kitabayashi N, Zhou XK et al. MicroRNA analysis as a potential diagnostic tool for papillary thyroid carcinoma. Mod Pathol 2008; 21 (9): 1139–1146. doi: 10.1038/modpathol.2008.105.

35. Ludvikova M, Kalfert D, Kholova I. Pathobiology of MicroRNAs and Their Emerging Role in Thyroid Fine-Needle Aspiration. Acta Cytol 2015; 59 (6): 435–444. doi: 10.1159/000442145.

36. Yu S, Liu Y, Wang J et al. Circulating microRNA profiles as potential biomarkers for diagnosis of papillary thyroid carcinoma. J Clin Endocrinol Metab 2012; 97 (6): 2084–2092.

37. Cheng G. Circulating miRNAs: roles in cancer diagnosis, prognosis and therapy. Adv Drug Deliv Rev 2015; 81: 75–93. doi: 10.1016/j.addr.2014.09.001.

38. Hu Y, Wang H, Chen E et al. Candidate microRNAs as biomarkers of thyroid carcinoma: a systematic review, meta-analysis, and experimental validation. Cancer Med 2016; 5 (9): 2602–2614. doi: 10.1002/cam4.811.

39. Lee LW, Zhang S, Etheridge A et al. Complexity of the microRNA repertoire revealed by next-generation sequencing. RNA 2010; 16 (11): 2170–2180. doi: 10.1261/rna.2225110.

40. Saiselet M, Gacquer D, Spinette A et al. New global analysis of the microRNA transcriptome of primary tumors and lymph node metastases of papillary thyroid cancer. BMC Genomics 2015; 16: 828. doi: 10.1186/s12864-015-2082-3.

41. Bartel DP. MicroRNAs: genomics, biogenesis, mechanism, and function. Cell 2004; 116 (2): 281–297.

42. Calin GA, Sevignani C, Dumitru CD 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.

43. Marini F, Luzi E, Brandi ML. MicroRNA Role in Thyroid Cancer Development. J Thyroid Res 2011; 2011: 407123. doi: 10.4061/2011/407123.

44. Ryan BM, Robles AI, Harris CC. Genetic variation in microRNA networks: the implications for cancer research. Nat Rev Cancer 2010; 10 (6): 389–402. doi: 10.1038/nrc2867.

45. Metias SM, Lianidou E, Yousef GM. MicroRNAs in clinical oncology: at the crossroads between promises and problems. J Clin Pathol 2009; 62 (9): 771–776.

46. Fabbri M, Ivan M, Cimmino A et al. Regulatory mechanisms of microRNAs involvement in cancer. Expert Opin Biol Ther 2007; 7 (7): 1009–1019.

47. Negrini M, Ferracin M, Sabbioni S et al. MicroRNAs in human cancer: from research to therapy. J Cell Sci 2007; 120 (Pt 11): 1833–1840.

48. Acunzo M, Romano G, Wernicke D et al. MicroRNA and cancer – a brief overview. Adv Biol Regul 2015; 57: 1–9. doi: 10.1016/j.jbior.2014.09.013.

49. Saiselet M, Pita JM, Augenlicht A et al. MiRNA expression and function in thyroid carcinomas: a comparative and critical analysis and a model for other cancers. Oncotarget 2016; 7 (32): 52475–52492. doi: 10.18632/oncotarget.9655.

50. Pallante P, Visone R, Croce CM et al. Deregulation of microRNA expression in follicular-cell-derived human thyroid carcinomas. Endocr Relat Cancer 2010; 17 (1): F91–F104. doi: 10.1677/ERC-09-0217.

51. Mancikova V, Castelblanco E, Pineiro-Yanez E et al. MicroRNA deep-sequencing reveals master regulators of follicular and papillary thyroid tumors. Mod Pathol 2015; 28 (6): 748–757.

52. Cancer Genome Atlas Research Network. Integrated genomic characterization of papillary thyroid carcinoma. Cell 2014; 159 (3): 676–690. doi: 10.1016/j.cell.2014.09. 050.

53. Yuan ZM, Yang ZL, Zheng Q. Deregulation of microRNA expression in thyroid tumors. J Zhejiang Univ Sci B 2014; 15 (3): 212–224. doi: 10.1631/jzus.B1300192.

54. Dettmer MS, Perren A, Moch H et al. MicroRNA profile of poorly differentiated thyroid carcinomas: new diag-nostic and prognostic insights. J Mol Endocrinol 2014; 52 (2): 181–189. doi: 10.1530/JME-13-0266.

55. Fuziwara CS, Kimura ET. MicroRNA Deregulation in Anaplastic Thyroid Cancer Biology. Int J Endocrinol 2014; 2014: 743450. doi: 10.1155/2014/743450.

56. Forte S, La Rosa C, Pecce V et al. The role of microRNAs in thyroid carcinomas. Anticancer Res 2015; 35 (4): 2037–2047.

57. Leonardi GC, Candido S, Carbone M et al. MicroRNAs and thyroid cancer: biological and clinical significance (Review). Int J Mol Med 2012; 30 (5): 991–999. doi: 10.3892/ijmm.2012.1089.

58. Li R, Liu J, Li Q et al. MiR-29a suppresses growth and metastasis in papillary thyroid carcinoma by targeting AKT3. Tumour Biol 2016; 37 (3): 3987–3996. doi: 10.1007/s13277-015-4165-9.

59. Lankenau MA, Patel R, Liyanarachchi S et al. MicroRNA-3151 inactivates TP53 in BRAF-mutated human malignancies. Proc Natl Acad Sci U S A 2015; 112 (49): E6744–E6751. doi: 10.1073/pnas.1520390112.

Labels
Paediatric clinical oncology Surgery Clinical oncology
Topics Journals
Login
Forgotten password

Enter the email address that you registered with. We will send you instructions on how to set a new password.

Login

Don‘t have an account?  Create new account

#ADS_BOTTOM_SCRIPTS#