MicroRNAs and apoptosis: implications in the molecular therapy of human disease

Abstract

SUMMARY1. MicroRNAs (miRNAs), the small non-coding RNAs of approximately 22 nucleotides, are now recognized as a very large family present throughout the genomes of plants and metazoans. These small transcripts modulate protein expression by binding to complementary or partially complementary target proteincoding mRNAs and targeting them for degradation or translational inhibition.2. The discovery of miRNAs has revolutionized our understanding of the mechanisms that regulate gene expression, with the addition of an entirely novel level of regulatory control. Considerable information on miRNAs has been accumulated in this rapidly evolving research field. We now know that miRNAs play pivotal roles in diverse processes, such as development and differentiation, control of cell proliferation and death, stress response and metabolism. Indeed, aberrant miRNA expression has been documented in human disease as well as in animal models, with evidence for a causative role in tumourigenesis.3. One of the most active fields of miRNA research is miRNA regulation of apoptosis, a programmed cell death implicated in many human diseases, such as cancer, Alzheimer's disease, hypertrophy and heart failure. Thus far, nearly 30 of 500 human miRNAs have been validated experimentally to regulate apoptosis; this number is likely to increase with future studies.4. The present review provides a comprehensive summary and analysis of the currently available data, focusing on the transcriptional controls, target genes and signalling pathways linking the apoptosis-regulating miRNAs and apoptotic cell death.

MicroRNA let-7c inhibits Bcl-xl expression and regulates ox-LDL-induced endothelial apoptosis

“…So we continue to assess other miRNAs involved in modulating ECs apoptosis. Among these up-regulated miRNAs, let-7c is known to be involved in the regulation of apoptosis (30). The ubiquitously expressed let-7 family was one of the first mammalian miRNAs to be identified.…”

Atrial Remodeling in Atrial Fibrillation and Some Related MicroRNAs

“…Equally as important, the impact on each regulated mRNA is subtle, but the combined effect is significant and produces measurable phenotypic results. miRNAs have been demonstrated to play important roles in diverse fundamental biological processes, including cell growth, cell death, cell differentiation, development and ageing [66,67,68]. They have also been implicated in a variety of pathological conditions, such as cancer, heart disease (myocardial infarction, cardiac hypertrophy/heart failure, arrhythmogenesis and AF) and Alzheimer’s disease [69,70,71,72,73,74,75].…”

Identification of microRNA-target interaction in APRIL-knockdown colorectal cancer cells

“…Due to the broad targeting ability, miRNAs have the potential to have central roles in physiological and pathological conditions, including cell differentiation, development, apoptosis and involving in the pathogenesis of several cancer types including colorectal cancer (CRC). [6][7][8] Recent studies have documented the association between the aberrant expression of miRNAs and the pathogenesis of CRC. Several miRNAs were differentially expressed between normal tissue and tumor subtypes, and microsatellite status for the majority of cancers could be correctly predicted based on miRNA expression profiles, indicating a potential role of miRNAs in diagnosis and treatment CBC.…”