Regulatory feedback loop between T3 and microRNAs in renal cancer

• miR-452 directly regulates the expression of THRB gene by binding to its 3’UTR.
• T3 downregulates the expression of miR-224/452 cluster and GABRE gene via TRs.
• miR-452 expression correlates with intratumoral T3 concentrations in renal cancer.
• T3 regulates the expression of miRNAs targeting THRB transcript.

microRNAs, short non-coding RNAs, influence key physiological processes, including hormonal regulation, by affecting the expression of genes. In this study we hypothesised that the expression of microRNAs targeting thyroid hormone pathway genes may be in turn regulated by thyroid hormone signalling. It is known that the expression of DIO1, a gene contributing to triiodothyronine (T3) signalling, is regulated by miR-224. Thus, we analysed mutual regulation between triiodothyronine pathway and miR-224/miR-452/GABRE cluster.Firstly, we found that miR-452 directly regulates the expression of thyroid hormone receptor TRβ1 in renal cancer cells. In turn, the expression of miR-224/452/GABRE cluster and other microRNAs targeting TRβ1 was influenced by T3 treatment and/or TR silencing. miR-452 expression correlated with intracellular T3 concentrations in renal tumours. In conclusion, we propose a new mechanism of feedback regulation, by which in renal cancer microRNAs regulate the expression of T3 pathway genes, while T3 in turn regulates expression of microRNAs.