Dicer expression and microRNA dysregulation associate with aggressive features in thyroid cancer.
By: Piril Erler, Xavier M Keutgen, Michael J Crowley, Tarek Zetoune, Anna Kundel, David Kleiman, Toni Beninato, Theresa Scognamiglio, Olivier Elemento, Rasa Zarnegar, Thomas J Fahey

Division of Endocrine and Minimally Invasive Surgery, Department of Surgery, New York Presbyterian Hospital-Weill Cornell Medical College, New York, NY.
2014-3-1; doi: 10.1016/j.surg.2014.08.007
Abstract

Background

Altered miRNA expression and down-regulation of Dicer has been shown in various cancers. We investigated Dicer expression and global miRNA environment in correlation with malignant features of thyroid tumors.

Methods

Dicer gene expression was assessed for 22 normal thyroids, 16 follicular adenomas, 28 papillary thyroid cancers (PTCs), 10 tall-cell variants of PTC, 11 follicular variants of PTC, as well as the four thyroid cell lines BCPAP, TPC1, KTC1, and TAD2 via quantitative polymerase chain reaction. BRAF((V600E)) mutation screening was completed for 31 neoplasms. Next-generation sequencing was performed on a subset of PTC and normal thyroid. Protein levels were assessed via Western blotting and immunohistochemistry.

Results

Dicer mRNA was down-regulated in malignant thyroid samples and cell lines compared with normal tissues, benign neoplasms, and the fetal cell line TAD2. Decreased Dicer gene expression in malignant tissues was correlated greatly with aggressive features: extrathyroidal extension, angiolymphatic invasion, multifocality, lymph node and distant metastasis, recurrence, and BRAF((V600E)) mutation. Conversely, increased levels of Dicer protein were observed in malignant tissues and cell lines. Sequencing yielded 19 differentially expressed miRNAs. Eight samples had a nonsignificant a global down-regulation in malignant tissues.

Conclusion

Dysregulation of Dicer and possibly altered expression of miRNAs are associated with aggressive features in thyroid cancers. These findings suggest that disruption in normal miRNA processing involving Dicer may play a role in thyroid cancer progression.



Published by Elsevier Inc.

PMID:25456905






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