BACKGROUND: MicroRNAs (miRNAs) are non-coding regulatory molecules 18-25 nucleotides in length that act as post-transcriptional regulators of gene expression. MiRNAs affect various biological processes including carcinogenesis. Deregulation of miRNAa expression has been described in a variety of tumors including papillary thyroid carcinoma (PTC). The aim of the present study was to investigate the role of selected miRNAs in PTC and find associations between miRNA expression and the BRAF (V600E) mutation. MATERIALS AND METHODS: The study group comprised a total of 62 patients with surgically treated PTC. The control group consisted of 30 patients with nodular goitre that were surgically treated in the same time period. The expression status of miR-146b, miR-181a, miR-187, miR-221 and miR-222 was determined using quantitative real-time PCR. BRAF mutation analysis was performed by PCR with reverse hybridization. RESULTS: MiR-146b, miR-181a, miR-187, miR-221 and miR-222 were up-regulated in PTC compared to normal thyroid gland tissue of the same patient. MiR-146b, miR-187, miR-221 and miR-222 were also up-regulated in PTC compared to nodular goitre. The recurrent tumors were statistically significantly associated with up-regulation of miR-221. The mutation V600E of BRAF gene was significantly associated with up-regulation of miR-146b and with down-regulation of miR-187. CONCLUSION: Over-expression of selected miRNAs in PTC compared to normal thyroid gland tissue and nodular goitre was found. Moreover, miR-221 may serve as a prognostic marker as its over-expression was significantly associated with recurrent tumors.

Department of Otorhinolaryngology and Head and Neck Surgery University Hospital Hradec Králové Králové Czech Republic

Department of Otorhinolaryngology and Head and Neck Surgery University Hospital Hradec Králové Králové Czech Republic;

Fingerland Department of Pathology University Hospital Hradec Králové Králové Czech Republic

Institute of Clinical Biochemistry and Diagnostics University Hospital Hradec Králové Králové Czech Republic

See more in PubMed

Braun J, Hoang-Vu C, Dralle H, Huttelmaier S. Downregulation of microRNAs directs the EMT and invasive potential of anaplastic thyroid carcinomas. Oncogene. 2010;29:4237–4244. doi: 10.1038/onc.2010.169. PubMed DOI

Keutgen XM, Filicori F, Crowley MJ, Wang Y, Scognamiglio T, Hoda R, Buitrago D, Cooper D, Zeiger MA, Zarnegar R, Elemento O, Fahey TJ. A Panel of four miRNAs accurately differentiates malignant from benign indeterminate thyroid lesions on fine needle aspiration. Clin Cancer Res. 2012;18:2032–2038. doi: 10.1158/1078-0432.CCR-11-2487. PubMed DOI

Lee JC, Gundara JS, Glover A, Serpell J, Sindhu SB. MicroRNA expression profiles in the management of papillary thyroid cancer. Oncologist. 2014;19:1141–1147. doi: 10.1634/theoncologist.2014-0135. PubMed DOI PMC

Chou CK, Liu RT, Kang HY. MicroRNA-146b: A novel biomarker and therapeutic target for human papillary thyroid cancer. Int J Mol Sci. 2017;18:636–645. doi: 10.3390/ijms18030636. PubMed DOI PMC

He H, Jazdzewski K, Li W, Liyanarachchi S, Nagy R, Volinia S, Calin GA, Liu C, Franssila K, Sester S, Kloos RT, Croce CM, de la Chapelle A. The role of microRNA genes in papillary thyroid carcinoma. PNAS. 2005;102:19075–19080. doi: 10.1073/pnas.0509603102. PubMed DOI PMC

Yip L, Kelly L, Shuai Y, Armstrong MJ, Nikiforov YE, Carty SE, Nikiforova MN. MicroRNA signature distinguishes the degree of aggressiveness of papillary thyroid carcinoma. Ann Surg Oncol. 2011;18:2035–2041. doi: 10.1245/s10434-011-1733-0. PubMed DOI PMC

Huang Y, Liao D, Pan L, Ye R, Li X, Wang S, Ye C, Chen L. Expressions of miRNAs in papillary thyroid carcinoma and their associations with BRAFV600E mutation. Eur J Endocrinol. 2013;168:675–681. doi: 10.1530/EJE-12-1029. PubMed DOI

Chruscik A, Lam AK. Clinical pathological impact of micro-RNAs in papillary thyroid carcinoma: A crucial review. Exp Mol Pathol. 2015;99:393–398. doi: 10.1016/j.yexmp.2015.08.013. PubMed DOI

Kalfert D, Pesta M, Kulda V, Topolcan O, Ryska A, Celakovky P, Ludvikova M. MicroRNA profile in site – specific head and neck squamous cell cancer. Anticancer Res. 2015;35:2455–2463. PubMed

Visone R, Russo L, Pallante P, De Martino I, Ferraro A, Leone V, Bonbone E, Petrocca F, Alder H, Croce CM, Fusco A. MicroRNAs (miR)-221 and miR-222, both overexpressed in human thyroid papillary carcinomas, regulate p27Kip1 protein levels and cell cycle. Endocrin Rel Cancer. 2007;14:791–798. doi: 10.1677/ERC-07-0129. PubMed DOI

Chen YT, Kitabayashi N, Zhou XK, Fandy TJ, Scognamiglio T. MicroRNA analysis as a potential diagnostic tool for papillary thyroid carcinoma. Modern Pathol. 2008;21:1139–1146. doi: 10.1038/modpathol.2008.105. PubMed DOI

Kovarikova H, Bubancova I, Laco J, Sieglova K, Vosmikova H, Dundr P, Nemejcova K, Michalek J, Vosmik M, Palicka V, Chmelarova M. Deregulation of selected microRNAs in sinonasal carcinoma: value of miR 21 as prognostic biomarker in sinonasal squamous cell carcinoma. Head Neck. 2017;39:2528–2536. doi: 10.1002/hed.24930. PubMed DOI

Laco J, Kovarikova H, Chmelarova M, Vosmikova H, Sieglova K, Bubancova I, Dundr P, Nemejcova K, Michalek J, Celakovsky P, Mottl R, Sirak I, Vosmik M, Marek I, Geryk T, Mejzlik J, Satankova J, Ryška A. Analysis of DNA methylation and microRNA expression in NUT (nuclear protein in testis) midline carcinoma of the sinonasal tract: a clinicopathological, immunohistochemical and molecular genetic study. Neoplasma. 2018;65:113–123. doi: 10.4149/neo_161122N581. PubMed DOI

Ludvikova M, Kalfert D, Kholova I. Pathobiology of microRNAs and their emerging role in thyroid fine-needle aspiration. Acta Cytol. 2015;59:435–444. doi: 10.1159/000442145. PubMed DOI

Ludvikova M, Kholova I, Kalfert D. Molecular aspects of thyroid tumors with emphasis on MicroRNA and their clinical implications. Clin Onkol. 2017;30:167–174. doi: 10.14735/amko2017167. PubMed DOI

Pallante P, Visone R, Ferracin M, Ferraro A, Berlingieri MT, Troncone G, Chiappetta G, Liu CG, Santoro M, Negrini M, Croce M, Fusco A. MicroRNA deregulation in human thyroid papillary carcinomas. Endocrin Rel Cancer. 2006;13:497–508. doi: 10.1677/erc.1.01209. PubMed DOI

Nikiforova MN, Tseng GC, Steward D, Diorit D, Nikiforov YE. MicroRNA expression profiling of thyroid tumors: Biological significance and diagnostic utility. J Clin Endocrinol Metab. 2008;93:1600–1608. doi: 10.1210/jc.2007-2696. PubMed DOI PMC

Huang Y, Yu S, Cao S, Yin Y, Hong A, Guan H, Li Y, Xiao A. MicroRNA-222 promotes invasion and metastasis of papillary thyroid cancer through targeting protein phosphatase 2 regulatory subunit B alpha expression. Thyroid. 2018;28:1162–1173. doi: 10.1089/thy.2017.0665. PubMed DOI

Schmittgen TD, Lee EJ, Jiang J, Sarkar A, Yang L, Elton TS, Chen C. Real-time PCR quantification of precursor and mature microRNA. Methods. 2008;44:31–38. doi: 10.1016/j.ymeth.2007.09.006. PubMed DOI PMC

D’cruz AK, Vaish R, Vaidya A, Nixon IJ, Williams MD, Poorten VV, López F, Angelos P, Shaha AR, Khafif A, Skalova A, Rinaldo A, Hunt JL, Ferlito A. Molecular markers in well-differentiated thyroid cancer. Eur Arch Oto-Rhino-Laryngol. 2018;275:1375–1384. doi: 10.1007/s00405-018-4944-1. PubMed DOI

Zembska A, Jawiarczyk-Przybylowska A, Wojtczak B, Bolanowski M. MicroRNA expression in the progression and aggressiveness of papillary thyroid carcinoma. Anticancer Res. 2019;39:33–40. doi: 10.21873/anticanres.13077. PubMed DOI

Wang X, Qi M. miR-718 is involved in malignancy of papillary thyroid cancer through repression of PDPK1. Pathol Res Pract. 2018;214:1787–1793. doi: 10.1016/j.prp.2018.08.022. PubMed DOI