MicroRNAs: Control and Loss of Control in Human Physiology and Disease

Abstract

Analysis of the human genome indicated that a large fraction of the genome sequences are RNAs that do not encode any proteins, also known as non-coding RNAs. MicroRNAs (miRNAs) are a group of small non-coding RNA molecules, with 20-22-nucleotide (nt) in length, and are predicted to control the activity of approximately 30% of all protein-coding genes in mammals. miRNAs play important roles in many diseases including cancer, cardiovascular disease, and immune disorders. The expression of miRNAs can be regulated by epigenetic modification, DNA copy number change, and genetic mutations. miRNAs can serve as a valuable therapeutic target for a large number of diseases. For miRNAs with oncogenic capabilities, potential therapies include miRNA silencing, antisense blocking, and miRNA modifications. For miRNAs with tumor suppression functions, overexpression of those miRNAs might be a useful strategy to inhibit tumor growth. In this review, we discuss the current progress of miRNA research, regulation of miRNA expression, prediction of miRNA targets, and regulatory role of miRNAs in human physiology and diseases, with a specific focus on miRNAs in pancreatic cancer, liver cancer, colon rectal cancer, cardiovascular disease, immune system, and infectious disease. This review provides valuable information for clinicians and researchers who want to recognize the newest advances in this new field and identify possible lines of investigation in miRNAs as important mediators in human physiology and diseases.

MicroRNA expression profiles associated with pancreatic adenocarcinoma and ampullary adenocarcinoma

“…After binding to the RISC microRNAs regulate gene expression posttranscriptionally by a binding of specific mRNA, depending on the target mRNA they can function as oncogene or tumor suppressor. [10][11][12][13][14][15][16][17][18][19] Several microRNAs or miR-families involved in stem cell signaling are identified, for example, miR-21 involved in self-renewal and apoptosis, the let-7 family and miR-200 family involved in pluripotency and cell differentiation. 34 The miR-200 family is down-regulated in cells undergoing epithelial-to-mesenchymal transition (EMT).…”

“…MicroRNAs regulate many genes known to play important roles in oncogenesis, angiogenesis and tissue differentiation. [10][11][12][13][14][15] In all, 1527 human microRNA sequences have been discovered to date and the number is increasing (miRBase. http:// www.mirbase.org, last accesses February 2012).…”

HepatomiRNoma: The proposal of a new network of targets for diagnosis, prognosis and therapy in hepatocellular carcinoma

“…Although miRNAs are able to negatively regulate the expression of target mRNAs, their expression is also regulated by different mechanisms such as specific translational regulation, methylation and histone deacetylation, DNA copy alteration and gene mutations affecting proteins involved in processing and maturation (Li et al, 2009a;Cummins and Velculescu, 2006). Furthermore, it has been reported that more than 50% of microRNA genes are often located in the fragile sites of chromosomes and in genomic regions which are prone to deletion, amplification and mutations (Corsini et al, 2012).…”

“…Alternatively, tumor suppressor microRNA, called anti-oncomiRs, are able to inhibit tumor growth by targeting oncogenes (Corsini et al, 2012;Visone and Croce, 2009). For these reasons, oncomiRs are up- (Corsini et al, 2012;Li et al, 2009a). For this reason, currently have been identified 23 miRNAs (miR-1, miR-9, miR-15b, miR-130b, miR-16, miR-18a, miR-21, miR-34, miR-92a, miR-101, miR-122, miR-129-2, miR-132, miR-195, miR-199a, miR-221, miR-222, miR-223, miR-224, miR-375, miR-500, miR-675, miR-885-5p) detectable in peripheral blood and tissues, which are involved in hepatocellular carcinoma development and progression and we can name them HepatomiRNoma as a whole.…”

A Database for TSSs of Human MicroRNAs

“…In the recent years, a major attention in molecular biology research is devoted over various short and long non-coding RNAs [15]. Of the various subclasses of non-coding RNAs, microRNAs (miRNAs) are the most thoroughly characterized subclass of short RNAs in the recent literature [2].…”