DataSheet_1_PRL1 Promotes Glioblastoma Invasion and Tumorigenesis via Activating USP36-Mediated Snail2 Deubiquitination.pdf

Regenerating liver phosphatase 1 (PRL1) is an established oncogene in various cancers, although its biological function and the underlying mechanisms in glioblastoma multiforme (GBM) remain unclear. Here, we showed that PRL1 was significantly upregulated in glioma tissues and cell lines, and positively correlated with the tumor grade. Consistently, ectopic expression of PRL1 in glioma cell lines significantly enhanced their tumorigenicity and invasion both in vitro and in vivo by promoting epithelial-mesenchymal transition (EMT). Conversely, knocking down PRL1 blocked EMT in GBM cells, and inhibited their invasion, migration and tumorigenic growth. Additionally, PRL1 also stabilized Snail2 through its deubiquitination by activating USP36, thus revealing Snail2 as a crucial mediator of the oncogenic effects of PRL1 in GBM pathogenesis. Finally, PRL1 protein levels were positively correlated with that of Snail2 and predicted poor outcome of GBMs. Collectively, our data support that PRL1 promotes GBM progression by activating USP36-mediated Snail2 deubiquitination. This novel PRL1/USP36/Snail2 axis may be a promising therapeutic target for glioblastoma.

再生性肝磷酸酶1（PRL1）是多种癌症中已确立的癌基因，尽管其在胶质母细胞瘤（GBM）中的生物学功能和潜在机制尚不明确。本研究中，我们发现PRL1在胶质瘤组织和细胞系中显著上调，且与肿瘤分级呈正相关。一致地，PRL1在胶质瘤细胞系中的异位表达显著增强了其在体外和体内的肿瘤生成性和侵袭性，这通过促进上皮间质转化（EMT）实现。相反，敲低PRL1可以阻断GBM细胞中的EMT，并抑制其侵袭、迁移和肿瘤生成性生长。此外，PRL1通过激活USP36来去泛素化，从而稳定Snail2，揭示了Snail2作为PRL1在GBM发病机制中致癌效应的关键介质。最后，PRL1蛋白水平与Snail2水平呈正相关，并预测GBM的预后不良。总之，我们的数据支持PRL1通过激活USP36介导的Snail2去泛素化来促进GBM的进展。这一新颖的PRL1/USP36/Snail2轴可能成为胶质母细胞瘤治疗的一个有希望的靶点。