ECE2013 Symposia Recent advances in the molecular study of endocrine tumours: microRNAs and more (3 abstracts)
Molecular Medicine Research Group, Hungarian Academy of Sciences and Semmelweis University, Budapest, Hungary.
The activin/transforming growth factor-β (TGF-β) is a family of evolutionary conserved polypeptides. Their role has been implicated in the regulation of embryonic development, reproduction and tumor formation.
Related to tumorigenesis TGF-β signaling inhibits cell proliferation at multiple levels by i) inducing the expression of tumor suppressors p15Ink4b and p21Waf1, ii) repressing oncogenic factors such as c-MYC and Id proteins, iii) by activation apoptosis and iv) inhibiting tumor growth by repressing hepatocyte growth factor (HGF), macrophage-stimulating protein (MSP) and TGF-α. Loss of members of the TGF-β signaling by somatic mutations or epigenetic events, such as DNA methylation or regulation by microRNA (miRNA) have been demonstrated to affect the signaling process. MmiRNAs are 1925 nucleotides long, non-coding RNA molecules that posttranscriptionally regulate gene expression via RNA interference. At least 3050% of all protein-coding genes are under regulation of miRNAs. Their expression is highly tissue-specific, and one miRNA affects the expression of several proteins and vice versa one protein is influenced by several miRNAs. Their role has been revealed in several physiological and pathological cellular processes including development, cell proliferation, differentiation, apoptosis and tumorigenesis. Therefore, this complex bidirectional link makes the mRNA-miRNA couples as an ideal targets for various therapuetical approaches. In addition, the biogenesis of miRNAs is also regulated by TGF-β, by regulating the maturation process of miRNAs. Members of TGF-β signaling are also targets for miRNAs. Hence auto-regulatory feedback loops between TGF-β and miRNAs influence the fate of tumor cells. Our aim is to review the crosstalk between TGF-β signaling and the miRNA machinery in order to discover bidirectional feed-back loops which contribute to the tumorigenesis process of endocrine glands, and to identify potential novel therapeutic targets.