Rodríguez-Mateo Cristina, Torres Belén, Gutiérrez Gabriel, Pintor-Toro José A
Department of Cell Signaling, Centro Andaluz de Biología Molecular y Medicina Regenerativa (CABIMER-CSIC), Avda Américo Vespucio s/n, Seville 41092, Spain.
Department of Genetics, Seville University, Seville 41080, Spain.
Cell Death Differ. 2017 May;24(5):785-797. doi: 10.1038/cdd.2017.9. Epub 2017 Feb 10.
Long non-coding RNAs (lncRNAs) are a class of regulatory genes that participate in a wide range of biological processes, including proliferation, differentiation and development, as well as in a broad spectrum of diseases. Although the role of lncRNAs in TGF-β-induced epithelial-to-mesenchymal transition (EMT) has been well established, little is known about the role of lncRNAs as immediate-early regulators of EMT. Here lnc-Spry1 is identified as an immediate-early regulator of EMT that is downregulated by TGF-β. It is also found that knockdown of lnc-Spry1 promotes a mesenchymal-like phenotype and results in increased cell migration and invasion. In addition, it is shown that lnc-Spry1 depletion preferentially affects the expression of TGF-β-regulated gene targets. Moreover, lnc-Spry1 associates with U2AF65 splicing factor, suggesting a role in alternative splicing. Depletion of lnc-Spry1 induces, as TGF-β, isoform switching of fibroblast growth factor receptors, resulting in FGF-2-sensitive cells. Taken together, these results show that lnc-Spry1 could act as an early mediator of TGF-β signaling and reveal different roles for a lncRNA in modulating transcriptional and posttranscriptional gene expression.
长链非编码RNA（lncRNAs）是一类调控基因，参与广泛的生物学过程，包括增殖、分化和发育，以及多种疾病。尽管lncRNAs在转化生长因子-β（TGF-β）诱导的上皮-间质转化（EMT）中的作用已得到充分证实，但关于lncRNAs作为EMT即时早期调节因子的作用却知之甚少。在此，lnc-Spry1被鉴定为一种受TGF-β下调的EMT即时早期调节因子。还发现敲低lnc-Spry1会促进间充质样表型，并导致细胞迁移和侵袭增加。此外，研究表明lnc-Spry1的缺失优先影响TGF-β调节的基因靶点的表达。此外，lnc-Spry1与U2AF65剪接因子相关联，表明其在可变剪接中发挥作用。lnc-Spry1的缺失会像TGF-β一样诱导成纤维细胞生长因子受体的异构体转换，从而产生对FGF-2敏感的细胞。综上所述，这些结果表明lnc-Spry1可能作为TGF-β信号传导的早期介质，并揭示了lncRNA在调节转录和转录后基因表达中的不同作用。
