LncRNA DGUOK-AS1 Promotes Bladder Cancer Progression by Enhancing EFTUD2 Stability.

IF 3.8 2区医学 Q2 ONCOLOGY

Cancer Research and Treatment Pub Date : 2025-09-18 DOI:10.4143/crt.2025.468

Wenwei Ying, Dingliang Li, Ninghan Feng, Wei Wei

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引用次数: 0

Abstract

Purpose: Long noncoding RNAs (lncRNAs) are increasingly being recognized to play important roles in cancer pathogenesis. However, the functional mechanisms of most lncRNAs remain poorly understood.

Materials and methods: RNA sequencing was performed to identify differentially expressed lncRNAs between non-muscle-invasive bladder cancer (NMIBC) and muscle-invasive bladder cancer (MIBC). In vitro and in vivo assays were conducted to investigate the functional role of lncRNA deoxyguanosine kinase 1 antisense RNA 1 (DGUOK-AS1). Meanwhile, RNA pull-down, RNA immunoprecipitation, co-immunoprecipitation, Western blot, and reverse transcription quantitative polymerase chain reaction assays were performed to explore the potential regulatory mechanisms of DGUOK-AS1 on its target genes.

Results: Our analysis revealed a significant upregulation of lncRNA DGUOK-AS1 in MIBC compared with NMIBC. Functionally, DGUOK-AS1 was found to enhance the proliferation and invasion of bladder cancer (BC) cells by interacting with elongation factor Tu GTP binding domain containing 2 (EFTUD2), a 116-kDa U5 small nuclear ribonucleoprotein component. Mechanistically, DGUOK-AS1 directly binds to EFTUD2 and the deubiquitinating protein valosin-containing protein-interacting protein 1, thereby shielding EFTUD2 from ubiquitination and subsequent degradation. Furthermore, EFTUD2 orchestrates the exclusion of cassette exon 11 from macrophage-stimulating 1 receptor, leading to the production of the RON∆165 isoform. This isoform activates the Akt/PKB signaling pathway, which is crucial for cancer progression.

Conclusion: DGUOK-AS1 drives BC progression via the EFTUD2/MST1R/Akt axis, offering a promising therapeutic target for BC treatment.

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LncRNA dguo - as1通过增强EFTUD2稳定性促进膀胱癌进展

目的：长链非编码rna （Long noncoding rna, lncRNAs）在肿瘤发病机制中发挥着重要作用。然而，大多数lncrna的功能机制仍然知之甚少。材料和方法：采用RNA测序方法鉴定非肌肉浸润性膀胱癌（NMIBC）和肌肉浸润性膀胱癌（MIBC）之间差异表达的lncRNAs。通过体外和体内实验研究lncRNA脱氧鸟苷激酶1反义RNA 1 （DGUOK-AS1）的功能作用。同时，通过RNA pull-down、RNA免疫沉淀、共免疫沉淀、Western blot、逆转录定量聚合酶链反应等方法，探讨dguo - as1对靶基因的潜在调控机制。结果：我们的分析显示，与NMIBC相比，lncRNA dguo - as1在MIBC中显著上调。在功能上，dguuk - as1通过与延伸因子Tu GTP结合域2 (EFTUD2)（一个116 kda的U5小核核糖核蛋白成分）相互作用，增强膀胱癌细胞的增殖和侵袭。在机制上，dguo - as1直接结合EFTUD2和去泛素化蛋白含缬氨酸蛋白相互作用蛋白1，从而屏蔽EFTUD2的泛素化和随后的降解。此外，EFTUD2协调排除巨噬细胞刺激1受体的盒外显子11，导致RON∆165异构体的产生。该异构体激活Akt/PKB信号通路，这对癌症进展至关重要。结论：dguo - as1通过EFTUD2/MST1R/Akt轴驱动BC进展，为BC治疗提供了一个有希望的治疗靶点。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Cancer Research and Treatment ONCOLOGY-

CiteScore

8.00

自引率

2.20%

发文量

126

审稿时长

>12 weeks

期刊介绍： Cancer Research and Treatment is a peer-reviewed open access publication of the Korean Cancer Association. It is published quarterly, one volume per year. Abbreviated title is Cancer Res Treat. It accepts manuscripts relevant to experimental and clinical cancer research. Subjects include carcinogenesis, tumor biology, molecular oncology, cancer genetics, tumor immunology, epidemiology, predictive markers and cancer prevention, pathology, cancer diagnosis, screening and therapies including chemotherapy, surgery, radiation therapy, immunotherapy, gene therapy, multimodality treatment and palliative care.