Down-regulation of microRNAs controlling tumourigenic factors in follicular thyroid carcinoma
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Down-regulation of microRNAs controlling tumourigenic factors in follicular thyroid carcinoma. / Rossing, Maria; Helweg-Larsen, Rehannah Borup; Henao Giraldo, Ricardo; Winther, Ole; Vikeså, Jonas; Niazi, Omid; Godballe, Christian; Krogdahl, Annelise; Glud, Martin; Sørensen, Christian Hjort; Kiss, Katalin; Bennedbæk, Finn Noe; Nielsen, Finn Cilius.
In: Journal of Molecular Endocrinology, Vol. 48, No. 1, 2012, p. 11-23.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Down-regulation of microRNAs controlling tumourigenic factors in follicular thyroid carcinoma
AU - Rossing, Maria
AU - Helweg-Larsen, Rehannah Borup
AU - Henao Giraldo, Ricardo
AU - Winther, Ole
AU - Vikeså, Jonas
AU - Niazi, Omid
AU - Godballe, Christian
AU - Krogdahl, Annelise
AU - Glud, Martin
AU - Sørensen, Christian Hjort
AU - Kiss, Katalin
AU - Bennedbæk, Finn Noe
AU - Nielsen, Finn Cilius
PY - 2012
Y1 - 2012
N2 - 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 characterized 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. 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 and by gene set enrichment analysis, we observed a significant identity between target mRNAs in FC and transcripts up-regulated in anaplastic carcinoma. 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 (NPV) of 83% (data generated by microarray platform) and of 92% (data generated by qRT-PCR platform). We conclude that follicular neoplasia is associated by 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.
AB - 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 characterized 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. 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 and by gene set enrichment analysis, we observed a significant identity between target mRNAs in FC and transcripts up-regulated in anaplastic carcinoma. 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 (NPV) of 83% (data generated by microarray platform) and of 92% (data generated by qRT-PCR platform). We conclude that follicular neoplasia is associated by 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.
U2 - 10.1530/JME-11-0039
DO - 10.1530/JME-11-0039
M3 - Journal article
C2 - 22049245
VL - 48
SP - 11
EP - 23
JO - Journal of Molecular Endocrinology
JF - Journal of Molecular Endocrinology
SN - 0952-5041
IS - 1
ER -
ID: 40143826