RESUMEN

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 TRß1 in renal cancer cells. In turn, the expression of miR-224/452/GABRE cluster and other microRNAs targeting TRß1 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.

Asunto(s)

Carcinoma de Células Renales/genética , Regulación Neoplásica de la Expresión Génica , Neoplasias Renales/genética , MicroARNs/genética , Receptores beta de Hormona Tiroidea/genética , Triyodotironina/genética , Carcinoma de Células Renales/metabolismo , Carcinoma de Células Renales/patología , Línea Celular Tumoral , Retroalimentación Fisiológica , Genes Reporteros , Humanos , Neoplasias Renales/metabolismo , Neoplasias Renales/patología , Luciferasas/genética , Luciferasas/metabolismo , MicroARNs/metabolismo , ARN Interferente Pequeño/genética , ARN Interferente Pequeño/metabolismo , Receptores de GABA-A/genética , Receptores de GABA-A/metabolismo , Transducción de Señal , Receptores beta de Hormona Tiroidea/antagonistas & inhibidores , Receptores beta de Hormona Tiroidea/metabolismo , Triyodotironina/biosíntesis , Triyodotironina/farmacología