Scholarlink

Background <p>The incidence of bladder cancer (BLCA) has steadily increased in recent years, and it is characterized by a high recurrence rate, often leading to poor patient outcomes. Cystoscopy and urinary cytology examinations have several limitations. Therefore, identifying biomarkers associated with the diagnosis and prognosis of BLCA is crucial.</p> Methods <p>A bladder cancer dataset was obtained from the Genome Expression Online (GEO) database. Differentially expressed genes (DEGs) were screened, and the selected genes were subjected to weighted gene coexpression network analysis (WGCNA), least absolute shrinkage and selection operator (LASSO) regression analysis, and protein‒protein interaction (PPI) network analysis to identify key genes involved in bladder cancer. The diagnostic value and prognostic significance of these key genes were validated using ROC curves, box plots, and survival curves. The infiltration levels of key genes in 28 immune cell types and their intercellular associations were analyzed. Molecular docking validated the binding affinity between MFAP4 and BLCA therapeutic drugs. MFAP4 expression in BLAC cell lines and SV-HUC-1 cells was detected via qPCR and WB analyses. MFAP4-overexpressing UM-UC-3 cells were generated using liposome-based transfection. Functional assays were performed on transfected UM-UC-3 cells. CCK8 assays were used to evaluate the effect of MFAP4 overexpression on doxorubicin sensitivity.</p> Results <p>This study revealed a total of 393 differentially expressed genes (DEGs), including 63 upregulated genes and 330 downregulated genes. Weighted gene coexpression network analysis (WGCNA) revealed seven coexpression modules, with the turquoise module showing the strongest correlation with bladder transitional cell carcinoma (BLCA). Intersection analysis between the differentially expressed genes and the turquoise module genes yielded 106 genes. Through LASSO regression analysis and protein‒protein interaction (PPI) network analysis, four key genes—COL6A1, COL16A1, CXCL12, and MFAP4—were selected. ROC curves, box plots, and survival curves revealed that MFAP4 had a high diagnostic value and was strongly associated with BLCA prognosis. Most cell types exhibited reduced levels of immune infiltration. Molecular docking analysis indicated that MFAP4 strongly binds to doxorubicin and gemcitabine, suggesting its potential as a drug target for BLCA. Compared with that in SV-HUC-1 cells, MFAP4 expression was significantly downregulated in BLCA cell lines. MFAP4 overexpression significantly inhibited the proliferation, migration, and invasion of UM-UC-3 cells, with both the IC50 values and cell survival rates being significantly lower than those of the other two groups.</p> Conclusion <p>The present study identified MFAP4 as a potential diagnostic and prognostic biomarker for bladder cancer (BLCA). MFAP4 is associated with proliferation, migration, and invasion of UM-UC-3 cells. MFAP4 overexpression enhances chemotherapy sensitivity in UM-UC-3 cells, potentially aiding in early diagnosis and providing novel therapeutic targets.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

Overexpression of MFAP4 inhibits the proliferation, migration, and invasion of bladder cancer cells

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年4月20日

查看全文
  • Wenxin Zhang,
  • Liangliang Dai,
  • Mingzhi Luo,
  • Honglei Shi

摘要

Background

The incidence of bladder cancer (BLCA) has steadily increased in recent years, and it is characterized by a high recurrence rate, often leading to poor patient outcomes. Cystoscopy and urinary cytology examinations have several limitations. Therefore, identifying biomarkers associated with the diagnosis and prognosis of BLCA is crucial.

Methods

A bladder cancer dataset was obtained from the Genome Expression Online (GEO) database. Differentially expressed genes (DEGs) were screened, and the selected genes were subjected to weighted gene coexpression network analysis (WGCNA), least absolute shrinkage and selection operator (LASSO) regression analysis, and protein‒protein interaction (PPI) network analysis to identify key genes involved in bladder cancer. The diagnostic value and prognostic significance of these key genes were validated using ROC curves, box plots, and survival curves. The infiltration levels of key genes in 28 immune cell types and their intercellular associations were analyzed. Molecular docking validated the binding affinity between MFAP4 and BLCA therapeutic drugs. MFAP4 expression in BLAC cell lines and SV-HUC-1 cells was detected via qPCR and WB analyses. MFAP4-overexpressing UM-UC-3 cells were generated using liposome-based transfection. Functional assays were performed on transfected UM-UC-3 cells. CCK8 assays were used to evaluate the effect of MFAP4 overexpression on doxorubicin sensitivity.

Results

This study revealed a total of 393 differentially expressed genes (DEGs), including 63 upregulated genes and 330 downregulated genes. Weighted gene coexpression network analysis (WGCNA) revealed seven coexpression modules, with the turquoise module showing the strongest correlation with bladder transitional cell carcinoma (BLCA). Intersection analysis between the differentially expressed genes and the turquoise module genes yielded 106 genes. Through LASSO regression analysis and protein‒protein interaction (PPI) network analysis, four key genes—COL6A1, COL16A1, CXCL12, and MFAP4—were selected. ROC curves, box plots, and survival curves revealed that MFAP4 had a high diagnostic value and was strongly associated with BLCA prognosis. Most cell types exhibited reduced levels of immune infiltration. Molecular docking analysis indicated that MFAP4 strongly binds to doxorubicin and gemcitabine, suggesting its potential as a drug target for BLCA. Compared with that in SV-HUC-1 cells, MFAP4 expression was significantly downregulated in BLCA cell lines. MFAP4 overexpression significantly inhibited the proliferation, migration, and invasion of UM-UC-3 cells, with both the IC50 values and cell survival rates being significantly lower than those of the other two groups.

Conclusion

The present study identified MFAP4 as a potential diagnostic and prognostic biomarker for bladder cancer (BLCA). MFAP4 is associated with proliferation, migration, and invasion of UM-UC-3 cells. MFAP4 overexpression enhances chemotherapy sensitivity in UM-UC-3 cells, potentially aiding in early diagnosis and providing novel therapeutic targets.