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.