Band 1, Heft 2014 -

MicroRNAs belong to a family of small (~23 nt) non-coding RNAs that mediate posttranscriptional gene silencing. They are emerging as important new regulators of differentiation and development. Knowledge of their role in pancreas and islet development, may help in developing a regenerative therapy for diabetes mellitus, a metabolic disorder affecting hundreds of millions of people worldwide. In this minireview, we summarize the latest evidence of the role these new regulators play in islet lineage development, aiming to attract more research into this important developmental regulators.

MicroRNAs (miRNAs) are endogenous single-stranded non-coding RNAs of about ~ 22 nucleotides which suppress gene expression by selectively binding to the 3’ non coding region (3’-UTR) of specific messenger RNAs through base-pairing. There are now more than 1600 human miRNAs annotated in the miRNA registry (http://microrna.sanger.ac.uk), but, at the moment, very few miRNAs have been well characterized and most of their roles remain unknown. miRNAs derive from transcripts that fold back on themselves to form distinctive hairpin structures, whereas the other types of endogenous small RNAs derive either from much longer hairpins that give rise to a greater diversity of small RNAs (siRNAs), or from bimolecular RNA duplexes (siRNAs), or from precursors without any suspected doublestranded character (piRNAs). The key step to understanding more about the possible functions of microRNA is to identify their mRNA targets. Recent studies have supported a role of miRNAs in the initiation and progression of human malignancies. Several groups have studied the global miRNA expression in cancer patients and found that miRNAs show different patterns of expression in normal and tumor tissues. The involvement of miRNAs in human cancer is probably due to the fact that >50% of miRNA genes are located at chromosomal regions, such as fragile sites or common break point sites, and regions of deletion or amplification that are generally altered in human tumors. Experimental evidence has shown that miRNA expression profiles enable the classification of poorly characterized human tumors that cannot be accurately classified using only the mRNA expression patterns. As a result, the miRs involved in the oncogenic transformation process are being investigated as novel biomarkers of disease detection and prognosis as well as potential therapeutic targets for human cancers. The aim of this review is to provide a general background regarding current knowledge about miRNA involvement in human pancreatic cancer and in the regulation of glucose metabolism.

Ever since the discovery of small non-coding RNAs, microRNAs have been identified to play a critical role in development and function of pancreatic insulin-producing beta cells. Research carried out until now demonstrates that microRNAs can specifically target key pancreatic transcription factors and signalling molecules. This in turn may influence changes in insulin production and secretion. microRNAs are also identified in insulin target organs that are altered as a result of hyperglycemia and insulin resistance. Recent studies demonstrate that microRNAs are not only confined to cells but are also detected in biological fluids including serum, plasma and urine. These data indicate that miRNAs may be looked upon having a dual role, as biomarkers and as regulators of disease. We review the existing literature in understanding the role of microRNAs in development, function and death of pancreatic beta cells as well as in the development of metabolic disease. We discuss the possible mechanisms that contribute to identifying the role of microRNAs as sensitive and efficient biomarkers to predict the progression of diabetes. Understanding tissue-specific microRNA signatures and their role as a cause or effect of diabetes would provide more information on progression of this disease.

Angiogenesis is the pathological process of forming new blood vessels from pre-existing vessels. It is one of the main features of many conditions such as cancer and inflammatory diseases. MicroRNAs (miRNAs) are small non-coding RNAs that regulate post-transcriptional gene expression. Recent studies have suggested that miRNAs play a significant role in angiogenesis. The study from Wang et al reported a novel angiomiR, miRNA-329, and its negative correlation with CD 146 expression in angiogenesis. These in vitro and in vivo studies introduce an appealing new way of treating angiogenesis by targeting CD146.