title: Dicer expression and microRNA dysregulation associate with aggressive features in thyroid cancer.
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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Division of Endocrine and Minimally Invasive Surgery, Department of Surgery, New York Presbyterian Hospital-Weill Cornell Medical College, New York, NY.
authors.forename: Piril
authors.initials: P
authors.lastname: Erler
authors.affiliation: Division of Endocrine and Minimally Invasive Surgery, Department of Surgery, New York Presbyterian Hospital-Weill Cornell Medical College, New York, NY.
authors.forename: Xavier M
authors.initials: XM
authors.lastname: Keutgen
authors.affiliation: Division of Endocrine and Minimally Invasive Surgery, Department of Surgery, New York Presbyterian Hospital-Weill Cornell Medical College, New York, NY.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Crowley
authors.affiliation: Division of Endocrine and Minimally Invasive Surgery, Department of Surgery, New York Presbyterian Hospital-Weill Cornell Medical College, New York, NY.
authors.forename: Tarek
authors.initials: T
authors.lastname: Zetoune
authors.affiliation: Division of Endocrine and Minimally Invasive Surgery, Department of Surgery, New York Presbyterian Hospital-Weill Cornell Medical College, New York, NY.
authors.forename: Anna
authors.initials: A
authors.lastname: Kundel
authors.affiliation: Division of Endocrine and Minimally Invasive Surgery, Department of Surgery, New York Presbyterian Hospital-Weill Cornell Medical College, New York, NY.
authors.forename: David
authors.initials: D
authors.lastname: Kleiman
authors.affiliation: Division of Endocrine and Minimally Invasive Surgery, Department of Surgery, New York Presbyterian Hospital-Weill Cornell Medical College, New York, NY.
authors.forename: Toni
authors.initials: T
authors.lastname: Beninato
authors.affiliation: Department of Pathology, New York Presbyterian Hospital-Weill Cornell Medical College, New York, NY.
authors.forename: Theresa
authors.initials: T
authors.lastname: Scognamiglio
authors.affiliation: Institute for Computational Biomedicine, New York Presbyterian Hospital-Weill Cornell Medical College, New York, NY.
authors.forename: Olivier
authors.initials: O
authors.lastname: Elemento
authors.affiliation: Division of Endocrine and Minimally Invasive Surgery, Department of Surgery, New York Presbyterian Hospital-Weill Cornell Medical College, New York, NY.
authors.forename: Rasa
authors.initials: R
authors.lastname: Zarnegar
authors.affiliation: 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.
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Fahey
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001707:Biopsy, Needle; D015153:Blotting, Western; D002277:Carcinoma / Q000235:genetics* / Q000473:pathology; D002291:Carcinoma, Papillary; D053487:DEAD-box RNA Helicases / Q000235:genetics*; D018450:Disease Progression; D015536:Down-Regulation; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D035683:MicroRNAs / Q000032:analysis / Q000235:genetics*; D008875:Middle Aged; D011379:Prognosis; D060888:Real-Time Polymerase Chain Reaction / Q000379:methods; D043244:Ribonuclease III / Q000235:genetics*; D012494:Sampling Studies; D000077273:Thyroid Cancer, Papillary; D013964:Thyroid Neoplasms / Q000235:genetics* / Q000473:pathology; D016610:Tissue Embedding; D055815:Young Adult
chemical_list: D035683:MicroRNAs; C408087:DICER1 protein, human; D043244:Ribonuclease III; D053487:DEAD-box RNA Helicases