miRNAs regulate expression and function of extracellular matrix molecules

MicroRNAs (miRNAs) are a family of small non-coding RNA molecules that are made up of 18–25 nucleotides that function in post-transcriptional gene regulation. The expression of miRNAs is highly conserved and essential in regulating many cellular processes including formation, maintenance and the remodelling of the extracellular matrix (ECM). In this review, we examine different ECM molecules and the miRNAs involved in regulating their abundance and how these changes influence cell phenotype. For example, miRNAs and their target messenger RNAs (mRNAs) are involved in cell adhesion, by regulating the synthesis and turnover of key ECM adhesion molecules and their receptors including cadherins, integrins and other non-integrin ECM receptors. Other miRNAs regulate the abundance of cytokines and growth factors which in turn stimulate cells to synthesize and secrete specialized ECMs. For example, miR-125a/b and miR-146a and their downstream target mRNAs influence the production of the epidermal growth factor family which has a significant impact on the nature of the ECM formed. miRNAs affect structural ECM proteins important in the assembly, composition and organization of the ECM. Proteins such as collagen, fibronectin, versican, and nephronectin are targeted by several miRNAs. miRNAs can also control the expression of proteins such as matrix metalloproteinases (MMPs) and tissue inhibitor of metalloproteinases (TIMPs), which are involved in ECM remodelling and are important for tissue development, cell motility and wound healing. It has become clear that many different miRNAs control the balance in ECM composition that determines normal tissue function and alterations in the expression of these miRNAs can lead to pathological consequences.