Journal of translational medicine · 2025
Smoking promotes the progression of bladder cancer through FOXM1/CKAP2L axis.
СтатьяПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод в очереди
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Wu Feixiang, Wu Shasha, Huang Yu, Xiao Xiao, Yu Haitao, Bai Xuesong, Zhang Chunlin, Feng Zhenwei, Li Li, Mei Yuhua, Li Xinyuan, Gou Xin
Аннотация
BACKGROUND: Smoking is a well-established risk factor for bladder cancer; however, the molecular mechanisms underlying this association remain unclear. This study aimed to elucidate the link between smoking and bladder cancer and identify the molecular mechanisms by which smoking promotes tumor progression.
METHODS: The relationships between smoking and bladder cancer were assessed with cross-sectional analyses and Mendelian randomization (MR) analyses. Bioinformatics analyses were conducted to identify the key genes involved in smoking-induced bladder cancer progression. Following treatment of bladder cancer cells with cigarette smoke extract (CSE), the effects of CKAP2L on proliferation and metastasis were evaluated using in vitro proliferation, migration, and invasion assays, as well as an in vivo subcutaneous tumor model. FOXM1 binding to the CKAP2L promoter was determined by chromatin immunoprecipitation (ChIP) assay.
RESULTS: Both cross-sectional and MR analyses confirmed the positive relationship between smoking and bladder cancer. Functional experiments revealed that CSE treatment promoted the proliferation and metastasis of bladder cancer cells. CKAP2L was identified as a key gene by bioinformatics analyses, and its expression was upregulated by CSE treatment. Additionally, CKAP2L knockdown inhibited cell proliferation, migration, and invasion; arrested the cell cycle at the S and G2/M phases; and regulated the expression of related proteins. Overexpression of CKAP2L exhibited the opposite results. The ChIP‒qPCR assay confirmed significant binding of FOXM1 to the CKAP2L promoter.
CONCLUSION: Smoking promoted bladder cancer progression by upregulating CKAP2L and FOXM1, which drive tumor progression via cell cycle regulation. This identifies the FOXM1/CKAP2L axis as a mechanism by which smoking facilitates bladder cancer progression.
METHODS: The relationships between smoking and bladder cancer were assessed with cross-sectional analyses and Mendelian randomization (MR) analyses. Bioinformatics analyses were conducted to identify the key genes involved in smoking-induced bladder cancer progression. Following treatment of bladder cancer cells with cigarette smoke extract (CSE), the effects of CKAP2L on proliferation and metastasis were evaluated using in vitro proliferation, migration, and invasion assays, as well as an in vivo subcutaneous tumor model. FOXM1 binding to the CKAP2L promoter was determined by chromatin immunoprecipitation (ChIP) assay.
RESULTS: Both cross-sectional and MR analyses confirmed the positive relationship between smoking and bladder cancer. Functional experiments revealed that CSE treatment promoted the proliferation and metastasis of bladder cancer cells. CKAP2L was identified as a key gene by bioinformatics analyses, and its expression was upregulated by CSE treatment. Additionally, CKAP2L knockdown inhibited cell proliferation, migration, and invasion; arrested the cell cycle at the S and G2/M phases; and regulated the expression of related proteins. Overexpression of CKAP2L exhibited the opposite results. The ChIP‒qPCR assay confirmed significant binding of FOXM1 to the CKAP2L promoter.
CONCLUSION: Smoking promoted bladder cancer progression by upregulating CKAP2L and FOXM1, which drive tumor progression via cell cycle regulation. This identifies the FOXM1/CKAP2L axis as a mechanism by which smoking facilitates bladder cancer progression.