IRAK2 overexpression restrains prostate cancer progression by regulation of TRAF6 ubiquitination

IF 4.4 2区生物学 Q2 CELL BIOLOGY

Cellular signalling Pub Date : 2024-11-15 DOI:10.1016/j.cellsig.2024.111508

Yunfeng Shi, Chengshuai Wu, Chengyue Wang, Ying Shen, Anqi Jiang, Kai Cao, Xiaowu Liu, Xinying Jiang, Zhong Lv

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引用次数: 0

Abstract

Prostate cancer is recognized as one of the most common tumors among men worldwide, yet the molecular mechanisms underlying its progression remain to be fully understood. In this study, we explored the role of interleukin-1 receptor-associated kinase 2 (IRAK2) in the progression of prostate cancer. We discovered that IRAK2 expression is downregulated in prostate cancer tissues and cells. Functional assays, including MTT, transwell assays, wound healing assays, and in vivo xenograft models, demonstrated that upregulation of IRAK2 significantly inhibited prostate cancer cell viability, migration, invasion, and tumor growth. Furthermore, we found that IRAK2 modulates the biological functions of prostate cancer by interacting with TNF receptor-associated factor 6 (TRAF6). Knockdown of TRAF6 reversed the suppressive effects of IRAK2 overexpression on prostate cancer cell progression. Additionally, IRAK2 was found to suppress the ubiquitination and degradation of TRAF6 in prostate cancer cells. IRAK2 also influenced the sensitivity of prostate cancer cells to docetaxel (DTX), and silencing IRAK2 reversed the anti-tumor effects of DTX on prostate cancer cells. Our findings suggest that IRAK2 functions as a tumor suppressor in prostate cancer and may serve as a potential therapeutic target for developing effective treatments for prostate cancer.

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IRAK2 过表达可通过调节 TRAF6 泛素化抑制前列腺癌的进展。

前列腺癌被认为是全球男性最常见的肿瘤之一，但其进展的分子机制仍有待全面了解。在这项研究中，我们探讨了白细胞介素-1受体相关激酶2（IRAK2）在前列腺癌进展中的作用。我们发现 IRAK2 在前列腺癌组织和细胞中表达下调。包括 MTT、透孔试验、伤口愈合试验和体内异种移植模型在内的功能试验表明，上调 IRAK2 能显著抑制前列腺癌细胞的活力、迁移、侵袭和肿瘤生长。此外，我们还发现IRAK2通过与TNF受体相关因子6（TRAF6）相互作用来调节前列腺癌的生物学功能。TRAF6的敲除逆转了IRAK2过表达对前列腺癌细胞进展的抑制作用。此外，IRAK2 还能抑制 TRAF6 在前列腺癌细胞中的泛素化和降解。IRAK2还影响前列腺癌细胞对多西他赛（DTX）的敏感性，沉默IRAK2可逆转DTX对前列腺癌细胞的抗肿瘤作用。我们的研究结果表明，IRAK2在前列腺癌中发挥着肿瘤抑制因子的作用，可能成为开发前列腺癌有效治疗方法的潜在治疗靶点。

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

Cellular signalling 生物-细胞生物学

CiteScore

8.40

自引率

0.00%

发文量

250

审稿时长

27 days

期刊介绍： Cellular Signalling publishes original research describing fundamental and clinical findings on the mechanisms, actions and structural components of cellular signalling systems in vitro and in vivo. Cellular Signalling aims at full length research papers defining signalling systems ranging from microorganisms to cells, tissues and higher organisms.