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Abstract：
BACKGROUND: Ubiquilin-4 (UBQLN4), a member of the ubiquilin family, has received limited attention in cancer research to date. Here, we investigated for the first time the functional role and mechanism of UBQLN4 in non-small cell lung cancer (NSCLC).
METHODS: The Cancer Genome Atlas (TCGA) database was employed to validate UBQLN4 as a differentially expressed gene. Expression differences of UBQLN4 in NSCLC cells and tissues were assessed using immunohistochemistry (IHC) experiment and western blotting (WB) experiment. Kaplan-Meier analysis was conducted to examine the association between UBQLN4 expression and NSCLC prognosis. Functional analyses of UBQLN4 were performed through cell counting kit-8 (CCK-8), colony formation, and transwell invasion assays. The impact of UBQLN4 on tumor-associated signaling pathways was assessed using the path scan intracellular signaling array. In vivo tumorigenesis experiments were conducted to further investigate the influence of UBQLN4 on tumor formation.
RESULTS: UBQLN4 exhibited up-regulation in both NSCLC tissues and cells. Additionally, over-expression of UBQLN4 was associated with an unfavorable prognosis in NSCLC patients. Functional loss analyses demonstrated that inhibiting UBQLN4 could suppress the proliferation and invasion of NSCLC cells in both in vitro and in vivo settings. Conversely, functional gain experiments yielded opposite results. Path scan intracellular signaling array results suggested that the role of UBQLN4 is associated with the PI3K/AKT pathway, a correlation substantiated by in vitro and in vivo tumorigenesis experiments.
CONCLUSIONS: We validated that UBQLN4 promotes proliferation and invasion of NSCLC cells by activating the PI3K/AKT pathway, thereby facilitating the progression of NSCLC. These findings underscore the potential of targeting UBQLN4 as a therapeutic strategy for NSCLC.
METHODS: The Cancer Genome Atlas (TCGA) database was employed to validate UBQLN4 as a differentially expressed gene. Expression differences of UBQLN4 in NSCLC cells and tissues were assessed using immunohistochemistry (IHC) experiment and western blotting (WB) experiment. Kaplan-Meier analysis was conducted to examine the association between UBQLN4 expression and NSCLC prognosis. Functional analyses of UBQLN4 were performed through cell counting kit-8 (CCK-8), colony formation, and transwell invasion assays. The impact of UBQLN4 on tumor-associated signaling pathways was assessed using the path scan intracellular signaling array. In vivo tumorigenesis experiments were conducted to further investigate the influence of UBQLN4 on tumor formation.
RESULTS: UBQLN4 exhibited up-regulation in both NSCLC tissues and cells. Additionally, over-expression of UBQLN4 was associated with an unfavorable prognosis in NSCLC patients. Functional loss analyses demonstrated that inhibiting UBQLN4 could suppress the proliferation and invasion of NSCLC cells in both in vitro and in vivo settings. Conversely, functional gain experiments yielded opposite results. Path scan intracellular signaling array results suggested that the role of UBQLN4 is associated with the PI3K/AKT pathway, a correlation substantiated by in vitro and in vivo tumorigenesis experiments.
CONCLUSIONS: We validated that UBQLN4 promotes proliferation and invasion of NSCLC cells by activating the PI3K/AKT pathway, thereby facilitating the progression of NSCLC. These findings underscore the potential of targeting UBQLN4 as a therapeutic strategy for NSCLC.
摘要：
背景：Ubiquilin-4（UBQLN4），ubiquilin家族的一员,迄今为止，在癌症研究中受到的关注有限。这里,我们首次研究了UBQLN4在非小细胞肺癌（NSCLC）中的功能作用和机制。
方法：使用癌症基因组图谱（TCGA）数据库来验证UBQLN4作为差异表达基因。使用免疫组织化学（IHC）实验和蛋白质印迹（WB）实验评估UBQLN4在NSCLC细胞和组织中的表达差异。进行Kaplan-Meier分析以检查UBQLN4表达与NSCLC预后之间的关联。通过细胞计数试剂盒-8（CCK-8）进行UBQLN4的功能分析，菌落形成,和transwell入侵测定。使用路径扫描细胞内信号传导阵列评估UBQLN4对肿瘤相关信号传导途径的影响。进行体内肿瘤发生实验以进一步研究UBQLN4对肿瘤形成的影响。
结果：UBQLN4在NSCLC组织和细胞中均表现出上调。此外,UBQLN4的过表达与NSCLC患者的不良预后相关.功能丧失分析表明，抑制UBQLN4可以在体外和体内环境中抑制NSCLC细胞的增殖和侵袭。相反，功能增益实验产生了相反的结果。路径扫描细胞内信号阵列结果表明，UBQLN4的作用与PI3K/AKT通路有关，通过体外和体内肿瘤发生实验证实的相关性。
结论：我们验证了UBQLN4通过激活PI3K/AKT通路促进NSCLC细胞增殖和侵袭，从而促进NSCLC的进展。这些发现强调了靶向UBQLN4作为NSCLC治疗策略的潜力。
方法：使用癌症基因组图谱（TCGA）数据库来验证UBQLN4作为差异表达基因。使用免疫组织化学（IHC）实验和蛋白质印迹（WB）实验评估UBQLN4在NSCLC细胞和组织中的表达差异。进行Kaplan-Meier分析以检查UBQLN4表达与NSCLC预后之间的关联。通过细胞计数试剂盒-8（CCK-8）进行UBQLN4的功能分析，菌落形成,和transwell入侵测定。使用路径扫描细胞内信号传导阵列评估UBQLN4对肿瘤相关信号传导途径的影响。进行体内肿瘤发生实验以进一步研究UBQLN4对肿瘤形成的影响。
结果：UBQLN4在NSCLC组织和细胞中均表现出上调。此外,UBQLN4的过表达与NSCLC患者的不良预后相关.功能丧失分析表明，抑制UBQLN4可以在体外和体内环境中抑制NSCLC细胞的增殖和侵袭。相反，功能增益实验产生了相反的结果。路径扫描细胞内信号阵列结果表明，UBQLN4的作用与PI3K/AKT通路有关，通过体外和体内肿瘤发生实验证实的相关性。
结论：我们验证了UBQLN4通过激活PI3K/AKT通路促进NSCLC细胞增殖和侵袭，从而促进NSCLC的进展。这些发现强调了靶向UBQLN4作为NSCLC治疗策略的潜力。
