MEN1 and microRNAs: The link between sporadic pituitary, parathyroid and adrenocortical tumors?

Sporadic tumors of the pituitary, parathyroids and adrenal cortex are unique, as their benign forms are very common, but malignant forms are exceptionally rare. Hereditary forms of these tumors occur in multiple endocrine neoplasia syndrome type 1 (MEN1). We hypothesize that the pathogenic link among the sporadic tumors of these organs of different germ layers might be represented by common molecular pathways involving the MEN1 gene and microRNAs (miR). miR-24 might be a microRNA linking the three tumor entities, but other candidates such as miR-142-3p and microRNAs forming the DLK1-MEG3 miRNA cluster might also be of importance.

Why is microRNA action tissue specific? A putative defense mechanism against growth disorders, tumor development or progression mediated by circulating microRNA?

MicroRNAs as endogenous mediators of RNA interference and epigenetic regulation are involved in the regulation of numerous basic physiological processes. Both their expression and action is tissue specific, as microRNA target different messenger RNA molecules in different tissues and have various actions. MicroRNAs are major players in tumor development and act as oncogenes and tumor suppressors that also depend on the cellular context. MicroRNA are secreted and are present in the circulation, and circulating microRNA might affect gene expression in various cells. We present a hypothesis on the relevance of tissue specific microRNA action supposing that it might be a putative defense mechanism preventing secreted microRNA-mediated uniform gene expression changes (e.g. inducing cell proliferation or inhibiting apoptosis) and thus growth disorders, tumor development or progression that would occur if all cells and tissues would respond in the same way to circulating microRNA.

Possible role for microRNAs as inter-species mediators of epigenetic information in disease pathogenesis: is the non-coding dark matter of the genome responsible for epigenetic interindividual or interspecies communication?

MicroRNAs are short non-coding RNA molecules involved in the posttranscriptional epigenetic regulation of gene expression. Recent data show that microRNAs can be found in body fluids, and these microRNAs might enter cells giving rise to a hormone like way of action. MicroRNAs released in body fluids might affect other individuals, and there are some data of potential cross-species action of microRNAs, as well. Here, the authors discuss hypotheses concerning the potential pathogenic relevance of interindividual and cross-species action of microRNAs including food-derived microRNAs. Supposing that microRNAs might traverse the gastrointestinal tract, microRNAs might wander via the food-chain and even master regulatory microRNAs might be envisaged that could influence gene expression in a wide range of species and might thereby link different species via common gene expression signatures. Since many microRNA genes are located in the non-protein coding "dark matter" of the genome, a novel function of this "dark matter" is raised regarding interindividual and cross-species epigenetic communication via information transfer by gene products coded by the non-protein coding part of the genome.