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DERL3通过调节TGFB1信号通路促进上皮-间质转化,从而推动透明细胞肾细胞癌的进展。

DERL3 facilitates the progression of clear cell renal cell carcinoma by promoting epithelial-mesenchymal transition via regulation of the TGFB1 pathway.

作者信息

Niu Chengtao, Cui Haodong, Sun Xintong, Yang Yuchang, Jiang Xue, Cong Zixiang, Zhang Yiming, Niu Zhihong, He Wei

机构信息

Department of Urology, Shandong Provincial Hospital, Shandong University, Jinan, Shandong, China.

Department of Urology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, China.

出版信息

PLoS One. 2025 Apr 29;20(4):e0322172. doi: 10.1371/journal.pone.0322172. eCollection 2025.

Abstract

BACKGROUND

Clear cell renal cell carcinoma (ccRCC) is a highly prevalent malignancy within the urinary system. The intrinsic heterogeneity and resistance to conventional chemotherapy and radiotherapy contribute to the poor prognosis of advanced ccRCC patients. DERL3, part of the Derlin protein family, was first identified for its critical role in endoplasmic reticulum stress. Subsequent studies have revealed its involvement in the progression of multiple tumor types; however, its role in ccRCC remains unclear.

METHODS

In this study, we utilized bioinformatics analysis and in vitro experimental approaches to investigate the role of DERL3 expression in the metastasis of renal clear cell carcinoma cells. Additionally, we analyzed the correlation between DERL3 expression and the prognosis of renal clear cell carcinoma patients, while exploring its potential mechanisms of action.

RESULTS

We demonstrate for the first time that DERL3 promotes tumor progression in ccRCC, showing significantly elevated expression, especially in metastatic ccRCC cell lines. Further studies suggest that this overexpression of DERL3 may promote the epithelial-mesenchymal transition in ccRCC by upregulating TGF-β1, thereby enhancing ccRCC metastasis.

CONCLUSION

In conclusion, our study clarifies the role and potential mechanisms of DERL3 in ccRCC progression, providing promising therapeutic avenues for improving the prognosis of ccRCC patients.

摘要

背景

透明细胞肾细胞癌(ccRCC)是泌尿系统中一种高度常见的恶性肿瘤。其内在的异质性以及对传统化疗和放疗的耐药性导致晚期ccRCC患者预后较差。DERL3是Derlin蛋白家族的一部分,最初因其在内质网应激中的关键作用而被发现。随后的研究表明它参与多种肿瘤类型的进展;然而,其在ccRCC中的作用仍不清楚。

方法

在本研究中,我们利用生物信息学分析和体外实验方法来研究DERL3表达在肾透明细胞癌细胞转移中的作用。此外,我们分析了DERL3表达与肾透明细胞癌患者预后之间的相关性,同时探索其潜在的作用机制。

结果

我们首次证明DERL3促进ccRCC中的肿瘤进展,其表达显著升高,尤其是在转移性ccRCC细胞系中。进一步的研究表明,DERL3的这种过表达可能通过上调TGF-β1促进ccRCC中的上皮-间质转化,从而增强ccRCC转移。

结论

总之,我们的研究阐明了DERL3在ccRCC进展中的作用和潜在机制,为改善ccRCC患者的预后提供了有前景的治疗途径。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4498/12040103/013b33dd46a8/pone.0322172.g001.jpg

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