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PUF60 通过调节 EGFR 稳定性促进胶质母细胞瘤进展。

PUF60 promotes glioblastoma progression through regulation of EGFR stability.

机构信息

The Affiliated Hospital of Medical School, Ningbo University, Ningbo, 315020, China.

The Affiliated Hospital of Medical School, Ningbo University, Ningbo, 315020, China.

出版信息

Biochem Biophys Res Commun. 2022 Dec 25;636(Pt 1):190-196. doi: 10.1016/j.bbrc.2022.10.082. Epub 2022 Oct 29.

Abstract

PUF60 (Poly (U) binding splicing factor 60 kDa), a nucleic acid-binding protein, has been shown to regulate transcription and links to tumorigenesis in various cancers. However, its biological role and function in glioblastoma remain unknown. In this study, we found that PUF60 is highly expressed in glioblastoma and correlated with poor prognosis. Furthermore, PUF60 knockdown significantly decreased the proliferation of glioblastoma cells in vitro and in vivo. Mechanistically, PUF60 could reduce the ubiquitination level of EGFR by transcriptionally regulating STUB1, an E3 ubiquitin ligase of EGFR, which lead to the activation of the EGFR-AKT pathway. Collectively, our study reveals the oncogenic role of PUF60 in glioblastoma and provides a potential therapeutic target for glioblastoma treatment.

摘要

PUF60(聚(U)结合剪接因子 60kDa)是一种核酸结合蛋白,已被证明在各种癌症中调节转录并与肿瘤发生有关。然而,它在胶质母细胞瘤中的生物学作用和功能尚不清楚。在这项研究中,我们发现 PUF60 在胶质母细胞瘤中高度表达,与预后不良相关。此外,PUF60 敲低显著降低了胶质母细胞瘤细胞在体外和体内的增殖。在机制上,PUF60 通过转录调控 EGFR 的 E3 泛素连接酶 STUB1,降低 EGFR 的泛素化水平,从而激活 EGFR-AKT 通路。总之,我们的研究揭示了 PUF60 在胶质母细胞瘤中的致癌作用,并为胶质母细胞瘤的治疗提供了一个潜在的治疗靶点。

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