MicroRNA-dependent targeting of the extracellular matrix as a mechanism of regulating cell behavior.

BACKGROUND: MicroRNAs are small noncoding RNAs which regulate gene expression at the posttranscriptional level by inducing mRNA degradation or translational repression. MicroRNA-dependent modulation of the extracellular matrix and its cellular receptors has emerged as a novel mechanism of regulating numerous matrix-dependent processes, including cell proliferation and apoptosis, cell adhesion and migration, cell differentiation and stem cell properties. SCOPE OF REVIEW: In this review, we will present different mechanisms by which microRNAs and extracellular matrix constituents mutually regulate their expression, and we will demonstrate how these expression changes affect cell behavior. We will also highlight the importance of dysregulated matrix-related microRNA expression for the pathogenesis of inflammatory and malignant disease, and discuss the potential for diagnostic and therapeutic applications. MAJOR CONCLUSIONS: MicroRNAs and matrix-dependent signal transduction processes form novel regulatory circuits, which profoundly affect cell behavior. As misexpression of microRNAs targeting extracellular matrix constituents is observed in a variety of diseases, a pharmacological intervention with these processes has therapeutic potential, as successfully demonstrated in vitro and in advanced animal models. However, a deeper mechanistic understanding is required to address potential side effects prior to clinical applications in humans. GENERAL SIGNIFICANCE: A full understanding of the role and function of microRNA-dependent regulation of the extracellular matrix may lead to new targeted therapies and new diagnostics for malignant and inflammatory diseases in humans. This article is part of a Special Issue entitled Matrix-mediated cell behaviour and properties.