MicroRNA regulation of integrins

MicroRNAs (miRNAs) are a family of small RNAs that are ∼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 α and a β subunit. Cumulatively, there are 18 α subunits and 8 β subunits that can combine to form 24 distinct αβ 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 α1 and α2 subunits, known to be regulated by specific miRNAs. Among the laminin ligand integrins, there are no integrin α subunits known to be regulated by miRNA. As for the RGD ligand integrins, integrin α5 is the only α subunit found to be regulated by miRNAs (miR-31, miR-17-92 cluster, and miR-148 b). Finally, among the α subunits that comprise the leukocyte-specific receptor ligand integrins, integrins αD, αL, αM, and αX have shown regulation by different miRNAs. As for the integrin β subunits, regulation by miRNAs has been reported for all but β5 and β6 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.