VDUP1 acts as a tumor suppressor gene in various cancers. VDUP1 is expressed at low levels in sporadic and ulcerative-colitis-associated colorectal cancer. However, the effects ofVDUP1deficiency on CAC remain unclear. In this study, we found thatVDUP1deficiency promoted CAC development in mice. Wild-type (WT) andVDUP1KO mice were used to investigate the role of VDUP1 in the development of azoxymethane (AOM)- and dextran sulfate sodium (DSS)-induced CAC. VDUP1 levels significantly decreased in the colonic tumor and adjacent nontumoral tissues of WT mice after AOM/DSS treatment. Moreover, AOM/DSS-treatedVDUP1KO mice exhibited a worse survival rate, disease activity index, and tumor burden than WT mice.VDUP1deficiency significantly induced cell proliferation and anti-apoptosis in tumor tissues ofVDUP1KO mice compared to WT littermates. Additionally, mRNA levels of interleukin-6 and tumor necrosis factor-alpha and active forms of signal transducer and activator of transcription 3 and nuclear factor-kappa B p65 were significantly increased in the tumor tissues ofVDUP1KO mice. Overall, this study demonstrated that the loss ofVDUP1promoted AOM/DSS-induced colon tumorigenesis in mice, highlighting the potential of VDUP1-targeting strategies for colon cancer prevention and treatment.
VDUP1在多种癌症中发挥肿瘤抑制基因的作用。在散发性及溃疡性结肠炎相关结直肠癌中，VDUP1呈低表达状态，但其缺失对结肠炎相关结直肠癌（CAC）的影响尚不明确。本研究通过对比野生型（WT）与VDUP1基因敲除（KO）小鼠，探讨VDUP1在氧化偶氮甲烷（AOM）与葡聚糖硫酸钠（DSS）诱导的CAC发生发展中的作用。结果显示，经AOM/DSS处理后，WT小鼠结肠肿瘤组织及癌旁正常组织中VDUP1表达水平显著下降。与WT小鼠相比，VDUP1 KO小鼠在接受AOM/DSS处理后表现出更低的生存率、更高的疾病活动指数及肿瘤负荷。组织学分析表明，VDUP1缺失显著促进了KO小鼠肿瘤组织的细胞增殖并抑制细胞凋亡。此外，KO小鼠肿瘤组织中白细胞介素-6、肿瘤坏死因子-α的mRNA水平显著升高，信号转导与转录激活因子3及核因子κB p65的活化形式表达明显增强。本研究证实VDUP1缺失会促进AOM/DSS诱导的小鼠结肠肿瘤发生，这为靶向VDUP1的结肠癌防治策略提供了理论依据。
肿瘤(癌症)患者之家