title: MicroRNA profiles in familial and sporadic medullary thyroid carcinoma: preliminary relationships with RET status and outcome.
abstract: BACKGROUND
  MicroRNAs (miRNAs) are involved in the pathogenesis of human cancers, including medullary thyroid carcinoma (MTC). The aim of this study was to test the hypothesis that different miRNA profiles are related to RET status and prognosis in patients with hereditary MTC (hMTC) and sporadic MTC (sMTC).
  
  
  METHODS
  We analyzed the expression of nine miRNAs (miR-21, miR-127, miR-154, miR-224, miR-323, miR-370, miR-9*, miR-183, and miR-375) by quantitative real-time-polymerase chain reaction in 34 cases of sMTC, 6 cases of hMTC, and 2 cases of C-cell hyperplasia (CCH). We also analyzed the immunohistochemical expression of PDCD4, an miR-21 gene target. sMTC (n=34) was genotyped for somatic RET and RAS mutations. Disease status was defined on the basis of the concentration of serum calcitonin at the latest follow-up and other parameters as indicated in the results.
  
  
  RESULTS
  MTC and CCH were both characterized by a significant overexpression of the whole set of miRNAs (the increase being 4.2-fold for miR-21, 6.7-fold for miR-127, 8.8-fold for miR-154, 6.6-fold for miR-224, 5.8-fold for miR-323, 6.1-fold for miR-370, 13-fold for miR-9*, 6.7-fold for miR-183, and 10.1 for miR-375, p<0.0001). PDCD4 expression was significantly downregulated in MTC samples, consistent with miR-21 upregulation. Significantly lower miR-127 levels were observed in sMTC carrying somatic RET mutations in comparison to sMTC carrying a wild-type RET. In sMTC and familial MTC, the miR-224 upregulation correlated with the absence of node metastases, lower stages at diagnosis, and with biochemical cure during follow-up.
  
  
  CONCLUSIONS
  miRNAs are significantly dysregulated in MTC, and this dysregulation is probably an early event in C-cell carcinogenesis. miR-224 upregulation could represent a prognostic biomarker associated with a better outcome in MTC patients.
authors: Endocrinology Unit, Department of Medicine, University of Padua, Via Aristide Gabelli 61, Padua, Italy.
authors: Caterina
authors: C
authors: Mian
authors: Gianmaria
authors: G
authors: Pennelli
authors: Matteo
authors: M
authors: Fassan
authors: Mariangela
authors: M
authors: Balistreri
authors: Susi
authors: S
authors: Barollo
authors: Elisabetta
authors: E
authors: Cavedon
authors: Francesca
authors: F
authors: Galuppini
authors: Marco
authors: M
authors: Pizzi
authors: Federica
authors: F
authors: Vianello
authors: Maria Rosa
authors: MR
authors: Pelizzo
authors: Maria Elisa
authors: ME
authors: Girelli
authors: Massimo
authors: M
authors: Rugge
authors: Giuseppe
authors: G
authors: Opocher
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D051017:Apoptosis Regulatory Proteins / Q000096:biosynthesis; D002116:Calcitonin / Q000097:blood; D018278:Carcinoma, Neuroendocrine; D005091:Exons; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000096:biosynthesis*; D008875:Middle Aged; D009154:Mutation; D051096:Proto-Oncogene Proteins c-ret / Q000235:genetics / Q000378:metabolism*; D016601:RNA-Binding Proteins / Q000096:biosynthesis; D013964:Thyroid Neoplasms / Q000235:genetics / Q000378:metabolism*; D059467:Transcriptome; D015854:Up-Regulation; D055815:Young Adult
chemical_list: D051017:Apoptosis Regulatory Proteins; D035683:MicroRNAs; C114487:PDCD4 protein, human; D016601:RNA-Binding Proteins; D002116:Calcitonin; D051096:Proto-Oncogene Proteins c-ret; C099282:RET protein, human