结直肠癌是全球癌症相关发病率和死亡率的主要贡献者。癌基因PTOV1与各种人类恶性肿瘤有关,然而其在CRC发病机制中的具体作用需要进一步阐明.
■我们的研究使用了一系列权威的生物信息学工具,比如TIMER,UCSCXena,GEO,人类蛋白质图谱,UALCAN,CIBERSORTx等人用于研究PTOV1对基因表达谱的复杂影响,诊断和预后生物标志物,肿瘤免疫学,信号通路,表观遗传改变,和基因突变。使用Western印迹和qRT-PCR进行基因表达验证。使用CCK-8测定评估CRC细胞的体外增殖和迁移潜力,菌落形成,和transwell迁移分析,分别。MSP用于评估PTOV1启动子区的甲基化状态。
■我们的结果表明,PTOV1表达增加之间存在显着关联,由启动子低甲基化驱动,CRC患者预后不良。升高的PTOV1水平与肿瘤微环境中多种免疫细胞亚群和免疫相关分子的富集呈正相关。体外实验表明,PTOV1敲低显著降低CRC细胞增殖,菌落形成,和移民,而异位PTOV1表达则有相反的作用。重要的是,显示PTOV1调节PI3K-AKT信号通路,显著影响AKT1的磷酸化和细胞周期调控因子P21和P27的表达。使用MK2206的AKT1磷酸化的药理学抑制有效地抵消了由PTOV1过表达诱导的增殖效应。
■PTOV1通过调节AKT1信号通路增强CRC细胞增殖的能力将其确立为潜在的治疗靶标和CRC预后分层的有希望的生物标志物。
UNASSIGNED: Colorectal cancer is a predominant contributor to global cancer-related morbidity and mortality. The oncogene PTOV1 has been linked to various human malignancies, yet its specific role in CRC pathogenesis requires further elucidation.
UNASSIGNED: Our study used a comprehensive array of authoritative bioinformatics tools, such as TIMER, UCSC Xena, GEO, Human Protein Atlas, UALCAN, CIBERSORTx and others which used to investigate the complex effects of PTOV1 on gene expression profiles, diagnostic and prognostic biomarkers, tumor immunology, signaling pathways, epigenetic alterations, and genetic mutations. Gene expression validation was conducted using Western blot and qRT-PCR. The in vitro proliferative and migratory potentials of CRC cells were evaluated using CCK-8 assays, colony formation, and transwell migration assays, respectively. MSP was applied to assess the methylation status of the PTOV1 promoter region.
UNASSIGNED: Our results reveal a significant association between increased PTOV1 expression, driven by promoter hypomethylation, and poor patient prognosis in CRC. Elevated PTOV1 levels were positively correlated with the enrichment of diverse immune cell subsets and immune-related molecules within the tumor microenvironment. In vitro assays demonstrated that PTOV1 knockdown markedly reduced CRC cell proliferation, colony formation, and migration, while ectopic PTOV1 expression had the opposite effect. Importantly, PTOV1 was shown to regulate the PI3K-AKT signaling pathway, significantly influencing the phosphorylation of AKT1 and the expression of cell cycle regulators P21 and
P27. The pharmacological inhibition of AKT1 phosphorylation using MK2206 effectively counteracted the proliferative effects induced by PTOV1 overexpression.
UNASSIGNED: The ability of PTOV1 to enhance CRC cell proliferation via modulation of the AKT1 signaling pathway establishes it as a potential therapeutic target and a promising biomarker for prognostic stratification in CRC.