MicroRNA Deregulation in Papillary Thyroid Cancer and Its Relationship With BRAF V600E Mutation

Overview

Journal In Vivo

Specialty Oncology

Date 2021 Jan 6

PMID 33402480

Citations 9

Authors

Petr celakovsky

Helena Kovarikova

Viktor Chrobok

Jan Mejzlik

Jan Laco

Hana Vosmikova

Marcela Chmelarova

Ales Ryska

Affiliations

Soon will be listed here.

Abstract

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.

Citing Articles

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The Application of microRNAs in Papillary Thyroid Cancer: A Bibliometric and Visualized Analysis.

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MicroRNA expression profiling of RAS-mutant thyroid tumors with follicular architecture: microRNA signatures to discriminate benign from malignant lesions.

Macerola E, Poma A, Vignali P, Proietti A, Torregrossa L, Ugolini C J Endocrinol Invest. 2023; 46(8):1651-1662.

PMID: 36749451 PMC: 10349002. DOI: 10.1007/s40618-023-02023-5.

References

Laco J, Kovarikova H, Chmelarova M, Vosmikova H, Sieglova K, Bubancova I . 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(1):113-123. DOI: 10.4149/neo_2018_161122N581. View

Nikiforova M, Tseng G, Steward D, Diorio D, Nikiforov Y . MicroRNA expression profiling of thyroid tumors: biological significance and diagnostic utility. J Clin Endocrinol Metab. 2008; 93(5):1600-8. PMC: 2386678. DOI: 10.1210/jc.2007-2696. View

Ludvikova M, Kalfert D, Kholova I . Pathobiology of MicroRNAs and Their Emerging Role in Thyroid Fine-Needle Aspiration. Acta Cytol. 2016; 59(6):435-44. DOI: 10.1159/000442145. View

Schmittgen T, Lee E, Jiang J, Sarkar A, Yang L, Elton T . Real-time PCR quantification of precursor and mature microRNA. Methods. 2007; 44(1):31-8. PMC: 2663046. DOI: 10.1016/j.ymeth.2007.09.006. View

Chruscik A, Lam A . Clinical pathological impacts of microRNAs in papillary thyroid carcinoma: A crucial review. Exp Mol Pathol. 2015; 99(3):393-8. DOI: 10.1016/j.yexmp.2015.08.013. View

Wang X, Qi M . miR-718 is involved in malignancy of papillary thyroid cancer through repression of PDPK1. Pathol Res Pract. 2018; 214(11):1787-1793. DOI: 10.1016/j.prp.2018.08.022. View

Zembska A, Jawiarczyk-Przybylowska A, Wojtczak B, Bolanowski M . MicroRNA Expression in the Progression and Aggressiveness of Papillary Thyroid Carcinoma. Anticancer Res. 2018; 39(1):33-40. DOI: 10.21873/anticanres.13077. View

Yip L, Kelly L, Shuai Y, Armstrong M, Nikiforov Y, Carty S . MicroRNA signature distinguishes the degree of aggressiveness of papillary thyroid carcinoma. Ann Surg Oncol. 2011; 18(7):2035-41. PMC: 4157306. DOI: 10.1245/s10434-011-1733-0. View

Keutgen X, Filicori F, Crowley M, Wang Y, Scognamiglio T, Hoda R . A panel of four miRNAs accurately differentiates malignant from benign indeterminate thyroid lesions on fine needle aspiration. Clin Cancer Res. 2012; 18(7):2032-8. DOI: 10.1158/1078-0432.CCR-11-2487. View

10.

He H, Jazdzewski K, Li W, Liyanarachchi S, Nagy R, Volinia S . The role of microRNA genes in papillary thyroid carcinoma. Proc Natl Acad Sci U S A. 2005; 102(52):19075-80. PMC: 1323209. DOI: 10.1073/pnas.0509603102. View

11.

Huang Y, Yu S, Cao S, Yin Y, Hong S, Guan H . MicroRNA-222 Promotes Invasion and Metastasis of Papillary Thyroid Cancer Through Targeting Protein Phosphatase 2 Regulatory Subunit B Alpha Expression. Thyroid. 2018; 28(9):1162-1173. DOI: 10.1089/thy.2017.0665. View

12.

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(29):4237-44. DOI: 10.1038/onc.2010.169. View

13.

DCruz A, Vaish R, Vaidya A, Nixon I, Williams M, Vander Poorten V . Molecular markers in well-differentiated thyroid cancer. Eur Arch Otorhinolaryngol. 2018; 275(6):1375-1384. DOI: 10.1007/s00405-018-4944-1. View

14.

Chou C, Liu R, Kang H . MicroRNA-146b: A Novel Biomarker and Therapeutic Target for Human Papillary Thyroid Cancer. Int J Mol Sci. 2017; 18(3). PMC: 5372649. DOI: 10.3390/ijms18030636. View

15.

Visone R, Russo L, Pallante P, De Martino I, Ferraro A, Leone V . MicroRNAs (miR)-221 and miR-222, both overexpressed in human thyroid papillary carcinomas, regulate p27Kip1 protein levels and cell cycle. Endocr Relat Cancer. 2007; 14(3):791-8. DOI: 10.1677/ERC-07-0129. View

16.

Kovarikova H, Bubancova I, Laco J, Sieglova K, Vosmikova H, Vosmik M . Deregulation of selected microRNAs in sinonasal carcinoma: Value of miR-21 as prognostic biomarker in sinonasal squamous cell carcinoma. Head Neck. 2017; 39(12):2528-2536. DOI: 10.1002/hed.24930. View

17.

Lee J, Gundara J, Glover A, Serpell J, Sidhu S . MicroRNA expression profiles in the management of papillary thyroid cancer. Oncologist. 2014; 19(11):1141-7. PMC: 4221366. DOI: 10.1634/theoncologist.2014-0135. View

18.

Ludvikova M, Kholova I, Kalfert D . [Molecular Aspects of Thyroid Tumors with Emphasis on MicroRNA and Their Clinical Implications]. Klin Onkol. 2017; 30(3):167-174. DOI: 10.14735/amko2017167. View

19.

Chen Y, Kitabayashi N, Zhou X, Fahey 3rd T, Scognamiglio T . MicroRNA analysis as a potential diagnostic tool for papillary thyroid carcinoma. Mod Pathol. 2008; 21(9):1139-46. DOI: 10.1038/modpathol.2008.105. View

20.

Huang Y, Liao D, Pan L, Ye R, Li X, Wang S . Expressions of miRNAs in papillary thyroid carcinoma and their associations with the BRAFV600E mutation. Eur J Endocrinol. 2013; 168(5):675-81. DOI: 10.1530/EJE-12-1029. View