miRNA-200c-3p targets talin-1 to regulate integrin-mediated cell adhesion.
miRNA-200c-3p targets talin-1 to regulate integrin-mediated cell adhesion.
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DOI：
10.1038/s41598-021-01143-3
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发表时间：
2021-11-03
影响因子：
4.6
通讯作者：
Shimaoka M
中科院分区：
文献类型：
--
作者：
Obeng G;Park EJ;Appiah MG;Kawamoto E;Gaowa A;Shimaoka M
细胞表面上的整合素介导细胞粘附至细胞外基质配体的能力受细胞内信号级联调节。在此信号传导过程中，募集到整合素胞质尾区的talin（TLN）作为主要衔接蛋白发挥关键作用，触发整合素活化。因此，TLN的细胞内水平被认为决定了整联蛋白介导的细胞功能。然而，TLN表达的表观遗传调控和随之而来的整合素激活的调节仍有待阐明。生物信息学分析使我们认为miR-200 c-3 p是一种靶向TLN 1的miRNA。为了测试这一点，我们已经产生了miR-200 c-3 p过表达和miR-200 c-3 p低表达的细胞系，包括HEK 293 T、HCT 116和LNCaP细胞。miR-200 c-3 p的过表达导致TLN 1的表达显著降低，这与整合素介导的细胞与纤连蛋白粘附的抑制有关。相反，内源性miR-200 c-3 p水平的降低导致TLN 1表达增加，并增强细胞与纤连蛋白的粘附和粘着斑形成。miR-200 c-3 p通过与TLN 1的3′-非翻译区（UTR）结合而靶向TLN 1。总之，我们的数据表明，miR-200 c-3 p有助于通过靶向TLN 1调节整合素活化和细胞粘附。
The ability of integrins on the cell surface to mediate cell adhesion to the extracellular matrix ligands is regulated by intracellular signaling cascades. During this signaling process, the talin (TLN) recruited to integrin cytoplasmic tails plays the critical role of the major adaptor protein to trigger integrin activation. Thus, intracellular levels of TLN are thought to determine integrin-mediated cellular functions. However, the epigenetic regulation of TLN expression and consequent modulation of integrin activation remain to be elucidated. Bioinformatics analysis led us to consider miR-200c-3p as a TLN1-targeting miRNA. To test this, we have generated miR-200c-3p-overexpressing and miR-200c-3p-underexpressing cell lines, including HEK293T, HCT116, and LNCaP cells. Overexpression of miR-200c-3p resulted in a remarkable decrease in the expression of TLN1, which was associated with the suppression of integrin-mediated cell adhesion to fibronectin. In contrast, the reduction in endogenous miR-200c-3p levels led to increased expression of TLN1 and enhanced cell adhesion to fibronectin and focal adhesion plaques formation. Moreover, miR-200c-3p was found to target TLN1 by binding to its 3′-untranslated region (UTR). Taken together, our data indicate that miR-200c-3p contributes to the regulation of integrin activation and cell adhesion via the targeting of TLN1.
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