Molecular medicine of microRNAs: structure, function and implications for diabetes

Abstract

MicroRNAs (miRNAs) are a family of endogenous small noncoding RNA molecules, of 19–28 nucleotides in length. In humans, up to 3% of all genes are estimated to encode these evolutionarily conserved sequences. miRNAs are thought to control expression of thousands of target mRNAs. Mammalian miRNAs generally negatively regulate gene expression by repressing translation, possibly through effects on mRNA stability and compartmentalisation, and/or the translation process itself. An extensive range of in silico and experimental techniques have been applied to our understanding of the occurrence and functional relevance of such sequences, and antisense technologies have been successfully used to control miRNA expression in vitro and in vivo. Interestingly, miRNAs have been identified in both normal and pathological conditions, including differentiation and development, metabolism, proliferation, cell death, viral infection and cancer. Of specific relevance and excitement to the area of diabetes research, miRNA regulation has been implicated in insulin secretion from pancreatic β-cells, diabetic heart conditions and nephropathy. Further analyses of miRNAs in vitro and in vivo will, undoubtedly, enable us determine their potential to be exploited as therapeutic targets in diabetes.

MicroRNAs and Their Role in Progressive Kidney Diseases

“…miR-122, a liver-expressed miR, was implicated in cholesterol and lipid metabolism and hence a potential target for the treatment of hypercholesterolemia (73,74). miR-124a was shown to play a role in glucose homeostasis (28,75) by targeting Rab27 and FOXA2 and MTPN. FOXA2 may regulate several targets that are relevant to diabetes, including insulin and potassium channel subunits, and also affect glucose homeostasis and pancreas development (28,75).…”

“…miR-124a was shown to play a role in glucose homeostasis (28,75) by targeting Rab27 and FOXA2 and MTPN. FOXA2 may regulate several targets that are relevant to diabetes, including insulin and potassium channel subunits, and also affect glucose homeostasis and pancreas development (28,75). It is interesting that 27 miR genes were reported to be located in nine of 19 insulin-dependent diabetes (IDDM) susceptibility loci (76).…”

“…Because miRs are important regulators of gene expression, misregulation or mutations of miRs are expected to play key roles in several diseases (5,11,27,28). Cancer was one of the first diseases to be related to abnormal expression or actions of miRs (5,11,27).…”

Relevance of circulating tumor cells, extracellular nucleic acids, and exosomes in breast cancer

“…MicroRNAs (miRNAs) are a family of endogenous small noncoding RNA molecules, of 19-28 nucleotides in length (reviewed: [144][145][146]). Over the past 2 years, since the first report of circulating microRNAs (miRNAs) associated with diffuse large B-cell lymphoma [147], circulating miRNAs have been reported in studies of a range of other cancer types.…”

microRNAs in Diabetic Kidney Disease

“…Nowadays, the critical role of microRNAs has been established in several cellular and biologic processes, such as proliferation, differentiation, and development, and in the regulation of genes relation to immune responses, cancer, and insulin secretion [16][17][18][19]. Because microRNAs are vital regulators of gene expression, aberrant of microRNAs are present in human diseases including cancer, hepatitis, and diabetes [17,[20][21][22][23]. There are also emerging reports about microRNAs in renal field.…”