FBXL6 regulates bladder cancer cell proliferation and migration via TNF⁃α signaling pathway

HUANG Ruoyu; WANG Xinghuan

doi:10.14188/j.1671-8852.2025.0051

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FBXL6 regulates bladder cancer cell proliferation and migration via TNF⁃α signaling pathway

更新时间：2026-11-06

- FBXL6 regulates bladder cancer cell proliferation and migration via TNF⁃α signaling pathway
- Medical Journal of Wuhan University Vol. 46, Issue 12, Pages: 1583-1589(2025)
- 作者机构：
  
  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
- 作者简介：
- 基金信息：
- DOI：10.14188/j.1671-8852.2025.0051
  CLC： R69
- Received：14 January 2025，
  
  Published：25 December 2025
- 稿件说明：
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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.

摘要

目的

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

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

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

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。

Abstract

Objective

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

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

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

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.

关键词

Keywords

references

COMPÉRAT E , AMIN M B , CATHOMAS R . Current best practice for bladder cancer: A narrative review of diagnostics and treatments [J ] . Lancet , 2022 400 ( 10364 ): 1712 ⁃ 1721 .

MARTINS⁃LIMA C , CHIANESE U , BENEDETTI R . Tumor microenvironment and epithelial⁃mesenchymal transition in bladder cancer: Cytokines in the game? [J ] . Front Mol Biosci , 2022 , 9 : 1070383 .

TING H K , CHEN C L , MENG E . Inflammatory regulation by TNF⁃α⁃activated adipose⁃derived stem cells in the Human bladder cancer microenvironment [J ] . Int J Mol Sci , 2021 , 22 ( 8 ): 3987 .

ZHANG J , LIN X T , YU H Q . Elevated FBXL6 expression in hepatocytes activates VRK2⁃transketolase⁃ROS⁃mTOR⁃mediated immune evasion and liver cancer metastasis in mice [J ] . Exp Mol Med , 2023 , 55 ( 10 ): 2162 ⁃ 2176 .

TANG Z , KANG B , LI C . GEPIA2: An enhanced web server for large⁃scale expression profiling and interactive analysis [J ] . Nucleic Acids Res , 2019 , 47 ( W1 ): W556 ⁃W560.

KIPREOS E T , PAGANO M . The F⁃box protein family [J ] . Genome Biol , 2000 , 1 ( 5 ): Reviews3002 .

TEKCHAM D S , CHEN D , LIU Y . F⁃box proteins and cancer: An update from functional and regulatory mechanism to therapeutic clinical prospects [J ] . Theranostics , 2020 , 10 ( 9 ): 4150 ⁃ 4167 .

TAO D , LOU S , HUANG W . Clinical and prognostic significance of FBXL6 expression in ovarian cancer [J ] . Gene , 2025 , 933 : 148978 .

MENG L , HU Y T , XU A M . F⁃box and leucine⁃rich repeat 6 promotes gastric cancer progression via the promotion of epithelial⁃mesenchymal transition [J ] . World J Gastrointest Oncol , 2023 , 15 ( 3 ): 490 ⁃ 503 .

LI Y , CUI K , ZHANG Q . FBXL6 degrades phosphorylated p53 to promote tumor growth [J ] . Cell Death Differ , 2021 , 28 ( 7 ): 2112 ⁃ 2125 .

SHI W , FENG L , DONG S . FBXL6 governs c⁃MYC to promote hepatocellular carcinoma through ubiquitination and stabilization of HSP90AA1 [J ] . Cell Commun Signal , 2020 , 18 ( 1 ): 100 .

BALKWILL F . TNF⁃alpha in promotion and progression of cancer [J ] . Cancer Metastasis Rev , 2006 , 25 ( 3 ): 409 ⁃ 416 .

LI H , LIU S , LI C . TNF Family⁃based signature predicts prognosis, tumor microenvironment, and molecular subtypes in bladder carcinoma [J ] . Front Cell Dev Biol , 2022 , 9 : 800967 .

WU Y , ZHOU B P . TNF⁃alpha/NF⁃kappaB/Snail pathway in cancer cell migration and invasion [J ] . Br J Cancer , 2010 , 102 ( 4 ): 639 ⁃ 644 .

MCGEACHY M J , CUA D J , GAFFEN S L . The IL⁃17 family of cytokines in health and disease [J ] . Immunity , 2019 , 50 ( 4 ): 892 ⁃ 906 .

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