Skip to main content
Top
Published in: Medical Oncology 5/2012

01-12-2012 | Original Paper

Overexpression of miR-221 is associated with aggressive clinicopathologic characteristics and the BRAF mutation in papillary thyroid carcinomas

Authors: Yi-Li Zhou, Chao Liu, Xuan-xuan Dai, Xiao-Hua Zhang, Ou-Chen Wang

Published in: Medical Oncology | Issue 5/2012

Login to get access

Abstract

Correlation between clinicopathogenetic features and the expression of specific miRNAs is unclear in papillary thyroid carcinoma (PTC). We therefore sought to assess whether miR-221 was associated with aggressive clinicopathologic characteristics and the BRAF mutation. We studied the expression levels of miR-221 using northern blot quantitated by scion image in 51 cases of PTCs. The status of BRAF of PTCs was analyzed through direct DNA sequencing. Mann–Whitney U test was used to analyze different expression of miR-221 in PTCs with distinct clinicopathogenetic characteristics including gender, age, tumor size, multifocality, extrathyroidal invasion, disease stages, node metastasis, and BRAF status. Compared with the normal thyroid tissues, the relative expression of miR-221 in tumor tissues was significantly upregulated (p < 0.001). Overexpression of miR-221 was significantly associated with extrathyroidal invasion (p = 0.001), lymph node metastasis (p = 0.046), advanced disease stages III–IV (p = 0.001), and the BRAF mutation (p = 0.014). While among BRAF wild tumors, miR-221 was only associated with extarthyroidal invasion, it showed strong association with all above aggressive features among BRAF mutation tumors. MiR-221 may be of potential importance in determining the aggressive properties of PTCs including the BRAF mutation, and it may further refine the risk stratification by BRAF mutation in PTCs.
Literature
1.
go back to reference Ito Y, Miyauchi A. Prognostic factors and therapeutic strategies for differentiated carcinomas of the thyroid. Endocr J. 2009;56(2):177–92.PubMedCrossRef Ito Y, Miyauchi A. Prognostic factors and therapeutic strategies for differentiated carcinomas of the thyroid. Endocr J. 2009;56(2):177–92.PubMedCrossRef
2.
go back to reference Xing M. BRAF mutation in papillary thyroid cancer: pathogenic role, molecular bases, and clinical implications. Endocr Rev. 2007;28(7):742–62.PubMedCrossRef Xing M. BRAF mutation in papillary thyroid cancer: pathogenic role, molecular bases, and clinical implications. Endocr Rev. 2007;28(7):742–62.PubMedCrossRef
3.
go back to reference Esquela-Kerscher A, Slack FJ. Oncomirs—microRNAs with a role in cancer. Nat Rev Cancer. 2006;6(4):259–69.PubMedCrossRef Esquela-Kerscher A, Slack FJ. Oncomirs—microRNAs with a role in cancer. Nat Rev Cancer. 2006;6(4):259–69.PubMedCrossRef
4.
go back to reference Pallante P, Visone R, Ferracin M, Ferraro A, Berlingieri MT, Troncone G, et al. MicroRNA deregulation in human thyroid papillary carcinomas. Endocr Relat Cancer. 2006;13(2):497–508.PubMedCrossRef Pallante P, Visone R, Ferracin M, Ferraro A, Berlingieri MT, Troncone G, et al. MicroRNA deregulation in human thyroid papillary carcinomas. Endocr Relat Cancer. 2006;13(2):497–508.PubMedCrossRef
5.
go back to reference Nikiforova MN, Tseng GC, Steward D, Diorio D, Nikiforov YE. MicroRNA expression profiling of thyroid tumors: biological significance and diagnostic utility. J Clin Endocrinol Metab. 2008;93(5):1600–8.PubMedCrossRef Nikiforova MN, Tseng GC, Steward D, Diorio D, Nikiforov YE. MicroRNA expression profiling of thyroid tumors: biological significance and diagnostic utility. J Clin Endocrinol Metab. 2008;93(5):1600–8.PubMedCrossRef
6.
go back to reference He H, Jazdzewski K, Li W, Liyanarachchi S, Nagy R, Volinia S, et al. The role of microRNA genes in papillary thyroid carcinoma. Proc Natl Acad Sci USA. 2005;102(52):19075–80.PubMedCrossRef He H, Jazdzewski K, Li W, Liyanarachchi S, Nagy R, Volinia S, et al. The role of microRNA genes in papillary thyroid carcinoma. Proc Natl Acad Sci USA. 2005;102(52):19075–80.PubMedCrossRef
7.
go back to reference Chen YT, Kitabayashi N, Zhou XK, Fahey TJ III, Scognamiglio T. MicroRNA analysis as a potential diagnostic tool for papillary thyroid carcinoma. Mod Pathol. 2008;21(9):1139–46.PubMedCrossRef Chen YT, Kitabayashi N, Zhou XK, Fahey TJ III, Scognamiglio T. MicroRNA analysis as a potential diagnostic tool for papillary thyroid carcinoma. Mod Pathol. 2008;21(9):1139–46.PubMedCrossRef
8.
go back to reference Chou CK, Chen RF, Chou FF, Chang HW, Chen YJ, Lee YF, et al. miR-146b is highly expressed in adult papillary thyroid carcinomas with high risk features including extrathyroidal invasion and the BRAF(V600E) mutation. Thyroid. 2010;20(5):489–94.PubMedCrossRef Chou CK, Chen RF, Chou FF, Chang HW, Chen YJ, Lee YF, et al. miR-146b is highly expressed in adult papillary thyroid carcinomas with high risk features including extrathyroidal invasion and the BRAF(V600E) mutation. Thyroid. 2010;20(5):489–94.PubMedCrossRef
9.
go back to reference Yip L, Kelly L, Shuai Y, Armstrong MJ, Nikiforov YE, Carty SE, et al. MicroRNA signature distinguishes the degree of aggressiveness of papillary thyroid carcinoma. Ann Surg Oncol. 2011;18:2035–41.PubMedCrossRef Yip L, Kelly L, Shuai Y, Armstrong MJ, Nikiforov YE, Carty SE, et al. MicroRNA signature distinguishes the degree of aggressiveness of papillary thyroid carcinoma. Ann Surg Oncol. 2011;18:2035–41.PubMedCrossRef
10.
go back to reference Gu LQ, Li FY, Zhao L, Liu Y, Zang XX, Wang TX, et al. BRAFV600E mutation and X-linked inhibitor of apoptosis expression in papillary thyroid carcinoma. Thyroid. 2009;19(4):347–54.PubMedCrossRef Gu LQ, Li FY, Zhao L, Liu Y, Zang XX, Wang TX, et al. BRAFV600E mutation and X-linked inhibitor of apoptosis expression in papillary thyroid carcinoma. Thyroid. 2009;19(4):347–54.PubMedCrossRef
11.
go back to reference Felli N, Fontana L, Pelosi E, Botta R, Bonci D, Facchiano F, et al. MicroRNAs 221 and 222 inhibit normal erythropoiesis and erythroleukemic cell growth via kit receptor down-modulation. Proc Natl Acad Sci USA. 2005;102(50):18081–6.PubMedCrossRef Felli N, Fontana L, Pelosi E, Botta R, Bonci D, Facchiano F, et al. MicroRNAs 221 and 222 inhibit normal erythropoiesis and erythroleukemic cell growth via kit receptor down-modulation. Proc Natl Acad Sci USA. 2005;102(50):18081–6.PubMedCrossRef
12.
go back to reference Mezentsev A, Seta F, Dunn MW, Ono N, Falck JR, Laniado-Schwartzman M. Eicosanoid regulation of vascular endothelial growth factor expression and angiogenesis in microvessel endothelial cells. J Biol Chem. 2002;277(21):18670–6.PubMedCrossRef Mezentsev A, Seta F, Dunn MW, Ono N, Falck JR, Laniado-Schwartzman M. Eicosanoid regulation of vascular endothelial growth factor expression and angiogenesis in microvessel endothelial cells. J Biol Chem. 2002;277(21):18670–6.PubMedCrossRef
14.
go back to reference Ugolini C, Giannini R, Lupi C, Salvatore G, Miccoli P, Proietti A, et al. Presence of BRAF V600E in very early stages of papillary thyroid carcinoma. Thyroid. 2007;17(5):381–8.PubMedCrossRef Ugolini C, Giannini R, Lupi C, Salvatore G, Miccoli P, Proietti A, et al. Presence of BRAF V600E in very early stages of papillary thyroid carcinoma. Thyroid. 2007;17(5):381–8.PubMedCrossRef
15.
go back to reference Visone R, Russo L, Pallante P, De Martino I, Ferraro A, Leone V, et al. 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.PubMedCrossRef Visone R, Russo L, Pallante P, De Martino I, Ferraro A, Leone V, et al. 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.PubMedCrossRef
16.
go back to reference Garofalo M, Di Leva G, Romano G, Nuovo G, Suh SS, Ngankeu A, et al. miR-221&222 regulate TRAIL resistance and enhance tumorigenicity through PTEN and TIMP3 downregulation. Cancer Cell. 2009;16(6):498–509.PubMedCrossRef Garofalo M, Di Leva G, Romano G, Nuovo G, Suh SS, Ngankeu A, et al. miR-221&222 regulate TRAIL resistance and enhance tumorigenicity through PTEN and TIMP3 downregulation. Cancer Cell. 2009;16(6):498–509.PubMedCrossRef
17.
go back to reference Pacifico F, Leonardi A. Role of NF-kappaB in thyroid cancer. Mol Cell Endocrinol. 2010;321(1):29–35.PubMedCrossRef Pacifico F, Leonardi A. Role of NF-kappaB in thyroid cancer. Mol Cell Endocrinol. 2010;321(1):29–35.PubMedCrossRef
18.
go back to reference Bommarito A, Richiusa P, Carissimi E, Pizzolanti G, Rodolico V, Zito G, et al. BRAFV600E mutation, TIMP-1 upregulation, and NF-kappaB activation: closing the loop on the papillary thyroid cancer trilogy. Endocr Relat Cancer. 2011;18(6):669–85.PubMedCrossRef Bommarito A, Richiusa P, Carissimi E, Pizzolanti G, Rodolico V, Zito G, et al. BRAFV600E mutation, TIMP-1 upregulation, and NF-kappaB activation: closing the loop on the papillary thyroid cancer trilogy. Endocr Relat Cancer. 2011;18(6):669–85.PubMedCrossRef
19.
go back to reference Galardi S, Mercatelli N, Farace MG, Ciafre SA. NF-kB and c-Jun induce the expression of the oncogenic miR-221 and miR-222 in prostate carcinoma and glioblastoma cells. Nucleic Acids Res. 2011;39(9):3892–902.PubMedCrossRef Galardi S, Mercatelli N, Farace MG, Ciafre SA. NF-kB and c-Jun induce the expression of the oncogenic miR-221 and miR-222 in prostate carcinoma and glioblastoma cells. Nucleic Acids Res. 2011;39(9):3892–902.PubMedCrossRef
20.
go back to reference Hu Z, Chen X, Zhao Y, Tian T, Jin G, Shu Y, et al. Serum microRNA signatures identified in a genome-wide serum microRNA expression profiling predict survival of non-small-cell lung cancer. J Clin Oncol. 2010;28(10):1721–6.PubMedCrossRef Hu Z, Chen X, Zhao Y, Tian T, Jin G, Shu Y, et al. Serum microRNA signatures identified in a genome-wide serum microRNA expression profiling predict survival of non-small-cell lung cancer. J Clin Oncol. 2010;28(10):1721–6.PubMedCrossRef
21.
go back to reference Asaga S, Kuo C, Nguyen T, Terpenning M, Giuliano AE, Hoon DS. Direct serum assay for microRNA-21 concentrations in early and advanced breast cancer. Clin Chem. 2011;57(1):84–91.PubMedCrossRef Asaga S, Kuo C, Nguyen T, Terpenning M, Giuliano AE, Hoon DS. Direct serum assay for microRNA-21 concentrations in early and advanced breast cancer. Clin Chem. 2011;57(1):84–91.PubMedCrossRef
22.
go back to reference Mazeh H, Mizrahi I, Halle D, Ilyayev N, Stojadinovic A, Trink B, et al. Development of a microRNA-based molecular assay for the detection of papillary thyroid carcinoma in aspiration biopsy samples. Thyroid. 2011;21(2):111–8.PubMedCrossRef Mazeh H, Mizrahi I, Halle D, Ilyayev N, Stojadinovic A, Trink B, et al. Development of a microRNA-based molecular assay for the detection of papillary thyroid carcinoma in aspiration biopsy samples. Thyroid. 2011;21(2):111–8.PubMedCrossRef
23.
go back to reference Kitano M, Rahbari R, Patterson EE, Xiong Y, Prasad NB, Wang Y, et al. Expression profiling of difficult-to-diagnose thyroid histologic subtypes shows distinct expression profiles and identify candidate diagnostic microRNAs. Ann Surg Oncol. 2011;18(12):3443–52.PubMedCrossRef Kitano M, Rahbari R, Patterson EE, Xiong Y, Prasad NB, Wang Y, et al. Expression profiling of difficult-to-diagnose thyroid histologic subtypes shows distinct expression profiles and identify candidate diagnostic microRNAs. Ann Surg Oncol. 2011;18(12):3443–52.PubMedCrossRef
Metadata
Title
Overexpression of miR-221 is associated with aggressive clinicopathologic characteristics and the BRAF mutation in papillary thyroid carcinomas
Authors
Yi-Li Zhou
Chao Liu
Xuan-xuan Dai
Xiao-Hua Zhang
Ou-Chen Wang
Publication date
01-12-2012
Publisher
Springer US
Published in
Medical Oncology / Issue 5/2012
Print ISSN: 1357-0560
Electronic ISSN: 1559-131X
DOI
https://doi.org/10.1007/s12032-012-0315-8

Other articles of this Issue 5/2012

Medical Oncology 5/2012 Go to the issue
Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin
Prof. Florian Limbourg
Prof. Anoop Chauhan
Developed by: Springer Medicine
Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.