Endocrine Abstracts

Type 1 deiodinase (D1) catalyses synthesis of triiodothyronine (T3) which regulates the expression of many tumor suppressor genes and oncogenes. We previously revealed that the expression of the whole pool of D1 transcripts was dramatically lowered in ccRCC tissues. One of the mechanims resulting in this aberration could be miRNA-mediated repression of target mRNAs. The aim of the study was 1) to analyze the expression of miRNA binding to 3′UTR of D1 in ccRCC; 2) to analyze the possible effect of T3 on the expression of miRNA in healthy cell lines and cancerous cell lines derived from ccRCC. Using semi-quantitative real-time PCR we have analyzed 34 samples of ccRCC tumors (T) and two types of control: the contralateral pole of the same kidney not infiltrated by cancer (C) and samples from patients suffering from other, nonneoplastic kidney abnormalities (N). Tissue samples were obtained with the permission of the local Ethical Committee of Human Studies. The effect of T3 was analyzed in cell lines: HK-2 (normal kidney), and Caki-2 (ccRCC).

Results: Bioinformatic analysis revealed the presence of multiple sites for microRNAs. We observed statistically significant (P<0.0001) over five fold increase in the expression of miR-224 and three fold increase in the expression of miR-383, in samples T compared to control samples C. The expression of miR-224 but not miR-383 was also higher in cancerous cell lines when compared to HK-2 (of 83% in Caki-2). We also observed that the expression of miR-224 and miR-383 was negatively regulated by T3 in both healthy HK-2 cell lines and Caki-2.

Conclusions: The lowered expression of D1 mRNA level may result from overexpression of miRNA. The expression of miRNA is negatively regulated by T3.