SFEBES2012 Symposia Small molecules, big effects: the emerging role of microRNAs (4 abstracts)
2nd Department of Medicine, Semmelweis University, Budapest, Hungary.
MicroRNAs are involved in the regulation of numerous cellular processes including cell proliferation, differentiation, apoptosis, and hormone secretion etc. Altered expression of microRNAs has been described in several tumours including endocrine neoplasms and microRNAs have been suggested to be involved in tumourigenesis at several levels. MicroRNAs may be classified as tumour suppressors and oncogenes (onco-miR) based on their relative under- or overexpression in tumour tissues, respectively. Differential expression of microRNAs has been established in different tumours of the thyroid, pituitary, adrenal, endocrine pancreas etc. MicroRNA biomarkers can be of great significance for the establishment of malignancy in tumours, whose histological diagnosis is unreliable, e.g. for differentiating benign and malignant follicular thyroid tumours, adrenocortical tumours and phaeochromocytomas. By the analysis of potential messenger RNA targets of microRNAs, novel molecular pathways might be identified that can be targets of anti-tumour therapy. The mTor signalling pathway has been thus shown to be relevant in childhood adrenocortical tumours, and everolimus effectively inhibited adrenocortical tumour growth in experimental models. We have shown the microRNA-mediated damage of cell cycle G2/M checkpoint in adrenocortical cancer and the relevance of Notch-signalling in recurrent phaeochromocytoma. MicroRNAs may also represent direct targets of anti-tumour therapy. The clinical use of microRNA-based therapy is complicated by several factors: i. microRNAs act in a tissue specific fashion and therefore a given microRNA may be oncogenic in one tissue, but tumour suppressor in another, ii. a single microRNA can influence numerous messenger RNAs (pleiotropy), iii. problems of administration.
Declaration of interest: There is no conflict of interest that could be perceived as prejudicing the impartiality of the research reported.
Funding: No specific grant from any funding agency in the public, commercial or not-for-profit sector.