1.武汉大学中南医院泌尿外科 湖北 武汉 430071
2.中国医学科学院武汉传染病与肿瘤研究中心 湖北 武汉 430071
黄若愚,男,1999—,医学硕士生,主要从事泌尿系肿瘤等方面的研究,E⁃mail:844710883@qq.com
王行环,男,1965—,教授,主任医师,主要从事泌尿系肿瘤等方面的研究,E⁃mail:wangxinghuan@whu.edu.cn
收稿:2025-01-14,
纸质出版:2025-12-25
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黄若愚,王行环.FBXL6通过TNF⁃α通路促进膀胱癌增殖和迁移[J].武汉大学学报(医学版),2025,46(12):1583-1589.
HUANG Ruoyu,WANG Xinghuan.FBXL6 regulates bladder cancer cell proliferation and migration via TNF⁃α signaling pathway[J].Medical Journal of Wuhan University,2025,46(12):1583-1589.
黄若愚,王行环.FBXL6通过TNF⁃α通路促进膀胱癌增殖和迁移[J].武汉大学学报(医学版),2025,46(12):1583-1589. DOI: 10.14188/j.1671-8852.2025.0051.
HUANG Ruoyu,WANG Xinghuan.FBXL6 regulates bladder cancer cell proliferation and migration via TNF⁃α signaling pathway[J].Medical Journal of Wuhan University,2025,46(12):1583-1589. DOI: 10.14188/j.1671-8852.2025.0051.
目的
2
探讨FBXL6在膀胱癌中的作用,特别是其通过调控肿瘤坏死因子(TNF)⁃α信号通路对膀胱癌细胞增殖和迁移的影响,评估FBXL6作为膀胱癌潜在预后标志物的价值。
方法
2
首先通过TCGA数据库分析了FBXL6在膀胱癌组织中的表达水平,并与临床预后数据进行了相关性分析。接着,采用小干扰RNA(siRNA)技术在5637细胞和T24细胞中敲低FBXL6表达,通过Western Blot(WB)和qRT⁃PCR验证其在蛋白质和mRNA水平的抑制效果。进一步通过MTT实验评估细胞增殖能力,并进行Transwell以及Wound healing实验评估细胞迁移能力。最后采用RNA测序(RNA⁃seq)分析FBXL6下游调控的分子通路,其中TNF⁃α信号通路最为显著,我们进一步选取其中关键蛋白,通过WB实验加以验证。
结果
2
TCGA数据分析显示,FBXL6在膀胱癌组织中的表达显著高于正常膀胱组织,且其高表达与膀胱癌患者的不良预后密切相关。细胞实验结果表明,敲低FBXL6后,膀胱癌细胞的增殖和迁移能力显著降低,过表达FBXL6则升高。RNA⁃seq分析进一步揭示,FBXL6通过调控TNF⁃α信号通路,促进了膀胱癌的发生和进展。
结论
2
本研究证明FBXL6在膀胱癌中的关键作用,特别是在促进细胞增殖和迁移方面。通过调节TNF⁃α信号通路,FBXL6可能促进膀胱癌的进展,提示FBXL6可能成为膀胱癌的预后标志物及潜在治疗靶点。
Objective
2
To investigate the role of FBXL6 in bladder cancer(BLCA)
focusing on its inference on cell proliferation and migration through regulation of the TNF⁃α signaling pathway
and evaluate its potential as a prognostic marker for BLCA.
Methods
2
FBXL6 expression levels in bladder cancer tissues were analyzed using data from The Cancer Genome Atlas (TCGA) database and correlated with clinical prognosis. FBXL6 expression was silenced in 5637 and T24 bladder cancer cells using small interfering RNA (siRNA)
and knockdown efficiency was confirmed at both protein and mRNA levels. Cell proliferation was assessed using the MTT assay
and cell migration was evaluated by Transwell and wound healing assays. RNA sequencing (RNA⁃seq) was performed to identify molecular pathways regulated by FBXL6
with a focus on TNF⁃α signaling pathway.
Results
2
TCGA analysis revealed that FBXL6 is significantly overexpressed in bladder cancer tissues compared to normal bladder tissues
and its high expression strongly correlates with a poor prognosis in bladder cancer patients. Functional assays demonstrated that FBXL6 silencing significantly inhibited cell proliferation and migration. RNA⁃seq analysis further indicated that FBXL6 promotes bladder cancer progression by modulating the TNF⁃α signaling pathway.
Conclusion
2
FBXL6 plays a pivotal role in bladder cancer progression by regulating cell proliferation and migration through the TNF⁃α signaling pathway. These findings suggest that FBXL6 could serve as a potential prognostic marker and therapeutic target for bladder cancer.
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