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Surgery. 2014 Dec;156(6):1342-50; discussion 1350. doi: 10.1016/j.surg.2014.08.007. Epub 2014 Nov 11.

Dicer expression and microRNA dysregulation associate with aggressive features in thyroid cancer.

Author information

1
Division of Endocrine and Minimally Invasive Surgery, Department of Surgery, New York Presbyterian Hospital-Weill Cornell Medical College, New York, NY.
2
Department of Pathology, New York Presbyterian Hospital-Weill Cornell Medical College, New York, NY.
3
Institute for Computational Biomedicine, New York Presbyterian Hospital-Weill Cornell Medical College, New York, NY.
4
Division of Endocrine and Minimally Invasive Surgery, Department of Surgery, New York Presbyterian Hospital-Weill Cornell Medical College, New York, NY. Electronic address: tjfahey@med.cornell.edu.

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.

PMID:
25456905
DOI:
10.1016/j.surg.2014.08.007
[Indexed for MEDLINE]
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