MicroRNA regulation of integrins

MicroRNAs (miRNAs) are a family of small RNAs that are similar to 20 nucleotides in length and are nontranslated. To date, more than 700 miRNAs have been identified, and their involvement in many essential cellular processes is now apparent. By binding with target messenger RNAs (mRNA), miRNAs are able to regulate both mRNA stability and mRNA translational efficiency. Integrins are a family of transmembrane proteins that both regulate cell matrix interactions and serve as receptors that mediate intracellular signaling and a variety of cellular processes, including inflammatory responses, immunoresponses, and tumorigenesis. Integrin expression may also be regulated by miRNAs, which can also modulate integrin signaling and function. Integrins are heterodimer adhesion proteins comprised of an alpha and a beta subunit. Cumulatively, there are 18 alpha subunits and 8 beta subunits that can combine to form 24 distinct alpha beta receptor complexes. In addition, each integrin can be classified into 1 of 4 groups based on its extracellular binding ligand: collagen, laminin, RGD (Arg-Gly-Asp) or leukocyte-specific receptors. Collagen ligand integrins include integrins alpha 1 and alpha 2 subunits, known to be regulated by specific miRNAs. Among the laminin ligand integrins, there are no integrin alpha subunits known to be regulated by miRNA. As for the RGD ligand integrins, integrin alpha 5 is the only alpha subunit found to be regulated by miRNAs (miR-31, miR-17-92 cluster, and miR-148 b). Finally, among the alpha subunits that comprise the leukocyte-specific receptor ligand integrins, integrins alpha D, alpha L, alpha M, and alpha X have shown regulation by different miRNAs. As for the integrin beta subunits, regulation by miRNAs has been reported for all but beta 5 and beta 6 to date. However, computational predictions suggest that numerous miRNAs potentially regulate a variety of target integrins. These predictions will undoubtedly guide future investigations of mechanisms underlying integrin expression mechanism and may ultimately yield new therapeutic tools.