U1297-Institut des Maladies Métaboliques et Cardiovasculaires (I2MC), Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Toulouse, F-31432 Toulouse, France.
Département de Biochimie Et Médecine Moléculaire, Faculté de Médecine, Université de Montréal, 2900 Édouard Montpetit Montréal, Montreal, QC H3T 1J4, Canada.
Int J Mol Sci. 2021 Dec 25;23(1):215. doi: 10.3390/ijms23010215.
Stau1 is a pluripotent RNA-binding protein that is responsible for the post-transcriptional regulation of a multitude of transcripts. Here, we observed that lung cancer patients with a high Stau1 expression have a longer recurrence free survival. Strikingly, Stau1 did not impair cell proliferation in vitro, but rather cell migration and cell adhesion. In vivo, Stau1 depletion favored tumor progression and metastases development. In addition, Stau1 depletion strongly impaired vessel maturation. Among a panel of candidate genes, we specifically identified the mRNA encoding the cell adhesion molecule Thrombospondin 1 (THBS1) as a new target for Staufen-mediated mRNA decay. Altogether, our results suggest that regulation of THBS1 expression by Stau1 may be a key process involved in lung cancer progression.
Stau1 是一种多能 RNA 结合蛋白,负责多种转录物的转录后调控。在这里,我们观察到高 Stau1 表达的肺癌患者有更长的无复发生存期。引人注目的是,Stau1 并没有在体外损害细胞增殖,而是损害了细胞迁移和细胞黏附。在体内,Stau1 的耗竭促进了肿瘤的进展和转移的发展。此外,Stau1 的耗竭强烈损害了血管成熟。在一组候选基因中,我们特别鉴定出编码细胞黏附分子血小板反应蛋白 1(THBS1)的 mRNA 是 Staufen 介导的 mRNA 降解的新靶点。总的来说,我们的结果表明,Stau1 对 THBS1 表达的调节可能是肺癌进展中涉及的一个关键过程。