دورية أكاديمية
Down-regulation of microRNAs controlling tumourigenic factors in follicular thyroid carcinoma.
| العنوان: | Down-regulation of microRNAs controlling tumourigenic factors in follicular thyroid carcinoma. |
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| المؤلفون: | Rossing M; Center for Genomic Medicine, University of Copenhagen, Rigshospitalet, DK - 2100 Copenhagen, Denmark., Borup R, Henao R, Winther O, Vikesaa J, Niazi O, Godballe C, Krogdahl A, Glud M, Hjort-Sørensen C, Kiss K, Bennedbæk FN, Nielsen FC |
| المصدر: | Journal of molecular endocrinology [J Mol Endocrinol] 2012 Jan 25; Vol. 48 (1), pp. 11-23. Date of Electronic Publication: 2012 Jan 25 (Print Publication: 2012). |
| نوع المنشور: | Journal Article; Research Support, Non-U.S. Gov't |
| اللغة: | English |
| بيانات الدورية: | Publisher: BioScientifica Country of Publication: England NLM ID: 8902617 Publication Model: Electronic-Print Cited Medium: Internet ISSN: 1479-6813 (Electronic) Linking ISSN: 09525041 NLM ISO Abbreviation: J Mol Endocrinol Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: Jan. 2011- : Bristol, UK : BioScientifica Original Publication: Bristol, U.K. : Journal of Endocrinology, Ltd., c1988- |
| مواضيع طبية MeSH: | Down-Regulation*, Adenocarcinoma, Follicular/*genetics , Cell Transformation, Neoplastic/*genetics , MicroRNAs/*genetics , Thyroid Neoplasms/*genetics, Adenocarcinoma, Follicular/classification ; Adenocarcinoma, Follicular/metabolism ; Adult ; Aged ; Cell Line, Tumor ; Cell Proliferation ; Cluster Analysis ; Computational Biology/methods ; Female ; Gene Expression Profiling ; Gene Expression Regulation, Neoplastic ; Humans ; Male ; Middle Aged ; Mutation ; Prognosis ; RNA, Messenger/metabolism ; Signal Transduction ; Thyroid Neoplasms/classification ; Thyroid Neoplasms/metabolism |
| مستخلص: | The molecular determinants of thyroid follicular nodules are incompletely understood and assessment of malignancy is a diagnostic challenge. Since microRNA (miRNA) analyses could provide new leads to malignant progression, we characterised the global miRNA expression in follicular adenoma (FA) and follicular carcinoma (FC). Comparison of carcinoma and adenoma with normal thyroid revealed 150 and 107 differentially expressed miRNAs respectively. Most miRNAs were down-regulated and especially miR-199b-5p and miR-144 which were essentially lost in the carcinomas. Integration of the changed miRNAs with differentially expressed mRNAs demonstrated an enrichment of seed sites among up-regulated transcripts encoding proteins implicated in thyroid tumourigenesis. This was substantiated by the demonstration that pre-miR-199b reduced proliferation when added to cultured follicular thyroid carcinoma cells. The down-regulated miRNAs in FC exhibited a substantial similarity with down-regulated miRNAs in anaplastic carcinoma (AC) and by gene set enrichment analysis, we observed a significant identity between target mRNAs in FC and transcripts up-regulated in AC. To examine the diagnostic potential of miRNA expression pattern in distinguishing malignant from benign nodules we employed a supervised learning algorithm and leave-one-out-cross-validation. By this procedure, FA and FC were identified with a negative predicted value of 83% (data generated by microarray platform) and of 92% (data generated by qRT-PCR platform). We conclude that follicular neoplasia is associated with major changes in miRNA expression that may promote malignant transformation by increasing the expression of transcripts encoding tumourigenic factors. Moreover, miRNA profiling may facilitate the diagnosis of carcinoma vs adenoma. |
| المشرفين على المادة: | 0 (MicroRNAs) 0 (RNA, Messenger) |
| تواريخ الأحداث: | Date Created: 20111104 Date Completed: 20120524 Latest Revision: 20120126 |
| رمز التحديث: | 20221213 |
| DOI: | 10.1530/JME-11-0039 |
| PMID: | 22049245 |
| قاعدة البيانات: | MEDLINE |
| تدمد: | 1479-6813 |
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| DOI: | 10.1530/JME-11-0039 |