Section of Pulmonary, Critical Care, Sleep and Allergy, Department of Medicine, University of Illinois at Chicago, Chicago, Ill., USA.
Transl Res. 2013 Sep;162(3):133-43. doi: 10.1016/j.trsl.2013.06.008. Epub 2013 Jul 13.
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.
微小 RNA（miRNA）是一类长度约为 20 个核苷酸的非翻译小 RNA。迄今为止，已经鉴定出超过 700 种 miRNA，它们参与许多重要的细胞过程已经显而易见。通过与靶信使 RNA（mRNA）结合，miRNA 能够调节 mRNA 的稳定性和翻译效率。整合素是一类跨膜蛋白，既能调节细胞基质相互作用，又能作为受体介导细胞内信号转导和多种细胞过程，包括炎症反应、免疫反应和肿瘤发生。整合素的表达也可能受到 miRNA 的调节，miRNA 也可以调节整合素信号和功能。整合素是由一个α和一个β亚基组成的异二聚体粘附蛋白。总共，有 18 个α亚基和 8 个β亚基可以结合形成 24 个不同的αβ受体复合物。此外，根据其细胞外结合配体，每个整合素可分为 4 组之一：胶原、层粘连蛋白、RGD（精氨酸-甘氨酸-天冬氨酸）或白细胞特异性受体。胶原配体整合素包括已知受特定 miRNA 调节的整合素α1 和α2 亚基。在层粘连蛋白配体整合素中，没有已知受 miRNA 调节的整合素α 亚基。至于 RGD 配体整合素，只有整合素α5 被发现受 miRNA 调节（miR-31、miR-17-92 簇和 miR-148b）。最后，在构成白细胞特异性受体配体整合素的α 亚基中，整合素αD、αL、αM 和αX 已被证明受不同 miRNA 的调节。至于整合素β 亚基，到目前为止，除了β5 和β6 之外，已经报道了 miRNA 的调节作用。然而，计算预测表明，许多 miRNA 可能调节多种靶整合素。这些预测无疑将指导未来对整合素表达机制的机制研究，并可能最终产生新的治疗工具。
