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

TitleDicer expression and microRNA dysregulation associate with aggressive features in thyroid cancer.
Publication TypeJournal Article
Year of Publication2014
AuthorsErler P, Keutgen XM, Crowley MJ, Zetoune T, Kundel A, Kleiman D, Beninato T, Scognamiglio T, Elemento O, Zarnegar R, Fahey TJ
Pagination1342-50; discussion 1350
Date Published2014 Dec
KeywordsAdolescent, Adult, Aged, Aged, 80 and over, Biopsy, Needle, Blotting, Western, Carcinoma, Carcinoma, Papillary, DEAD-box RNA Helicases, Disease Progression, Down-Regulation, Female, Gene Expression Regulation, Neoplastic, Humans, Immunohistochemistry, Male, MicroRNAs, Middle Aged, Prognosis, Real-Time Polymerase Chain Reaction, Ribonuclease III, Sampling Studies, Thyroid Cancer, Papillary, Thyroid Neoplasms, Tissue Embedding, Young Adult

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.

Alternate JournalSurgery
PubMed ID25456905