研究动态
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FGF13A与NPM1和UBF相互作用,并抑制膀胱癌细胞的侵袭。

FGF13A interacts with NPM1 and UBF and inhibits the invasion of bladder cancer cells.

发表日期:2023 Aug 18
作者: Dong Han, Lei Guan, Yingying Zhang, Huan Yang, Libu Si, Tongyu Jia, Yangyang Wu, Kaikai Lv, Tao Song, Guang Yang
来源: TROPICAL MEDICINE & INTERNATIONAL HEALTH

摘要:

膀胱癌(BC)浸润是影响患者预后和生活质量的关键因素。然而,膀胱癌浸润的潜在机制尚不清楚。成纤维细胞生长因子13(FGF13)是一种非分泌型FGF,在多种肿瘤中被异常表达,并参与肿瘤发展,但其与膀胱癌的潜在关联尚未研究。在这里,我们报道了FGF13A的表达在膀胱癌患者中下调,并与肿瘤浸润呈负相关。此外,我们证明了FGF13A的过表达可以抑制BC 5637和T24细胞的迁移和浸润。我们还证实了FGF13A在核仁中的定位,并与核蛋白NPM1和UBP相互作用。随后,我们确定了FGF13A的氨基端区域对其在核仁的定位和与NPM1的相互作用至关重要。此外,我们发现FGF13A通过其氨基端区域抑制新生核糖体RNA的生成,并通过此作用抑制膀胱癌细胞的迁移和浸润。我们的研究首次建立了FGF13A表达与膀胱癌的发生和进展之间的相关性,为了解FGF13A在膀胱癌发展中的作用提供了新的见解。版权所有 © 2023。Elsevier Inc. 发表。
Bladder cancer (BC) invasion is a critical factor that impacts the prognosis and quality of life of patients. However, the underlying mechanisms of BC invasion is far from clear. Fibroblast growth factor 13 (FGF13), a non-secretory FGF, has been found to be ectopically expressed in various tumors and implicated in tumor development, but its potential association to BC has not been investigated. Here, we reported that the expression of FGF13A, one nucleolar isoform of FGF13, was downregulated in BC patients and negatively associated with tumor invasion. Additionally, we demonstrated that overexpression of FGF13A could inhibit the migration and invasion of BC 5637 and T24 cells. We also confirmed the localization of FGF13A in the nucleolus and its interaction with nucleoproteins NPM1 and UBP. Subsequently, we identified that the N-terminal region of FGF13A was essential for its nucleolus location and interaction with NPM1. Furthermore, we found that FGF13A inhibited the generation of nascent ribosomal RNA and suppressed the migration and invasion of BC cells through its N-terminal region. Our research establishes, for the first time, a correlation between the expression of FGF13A and the onset and progression of BC. This provides novel insights into the role of FGF13A in the development of BC.Copyright © 2023. Published by Elsevier Inc.