背景:非小细胞肺癌(NSCLC)是肺癌的一种恶性形式,通过确定关键治疗靶点可以改善其预后。因此,这项研究调查了F-boxOnly蛋白33(FBXO33)在NSCLC中的潜在作用。
方法:使用阿拉巴马大学伯明翰癌症数据分析门户(UALCAN)预测确定FBXO33在NSCLC中的表达水平,并通过Kaplan-Meier生存分析分析其与总生存期(OS)的相关性。这些结果通过定量聚合酶链反应(qPCR)进行了验证,蛋白质印迹(WB),和免疫荧光(IF)。我们通过过表达或敲低调节FBXO33表达,并分析其对细胞生长的影响,扩散,迁移,入侵,NSCLC细胞系的干细胞特性。此外,研究了FBXO33与骨髓细胞瘤病(Myc)之间的相互作用及其对Myc泛素化的影响。使用体内NSCLC异种移植模型来证实体内实验结果。
结果:研究发现,在非小细胞肺癌中FBXO33表达与OS呈负相关。较低的FBXO33表达增强了生长,扩散,迁移,入侵,NSCLC细胞系的干细胞特性。FBXO33与Myc相互作用以促进其泛素化和随后的降解,抑制NSCLC的发展。
结论:FBXO33在非小细胞肺癌中低水平表达,与较低的OS相关。FBXO33过表达促进Myc泛素化和降解,抑制肿瘤细胞增殖,迁移和干性特征,从而阻碍NSCLC进展。
BACKGROUND: Non-small cell lung cancer (NSCLC) is a malignant form of lung cancer, and its prognosis could be improved by identifying key therapeutic targets. Thus, this study investigates the potential role of F-box Only Protein 33 (FBXO33) in NSCLC.
METHODS: The expression levels of FBXO33 in NSCLC were determined using University of Alabama at Birmingham Cancer Data Analysis Portal (UALCAN) prediction, and its correlation with overall survival (OS) was analyzed via Kaplan-Meier survival analysis. These results were validated through quantitative polymerase chain reaction (qPCR), western blot (WB), and immunofluorescence (IF). We modulated FBXO33 expression by overexpression or knockdown and analyzed its effects on cell growth, proliferation, migration, invasion, and
stemness characteristics in NSCLC cell lines. Additionally, the interaction between FBXO33 and Myelocytomatosis (Myc) and its impact on Myc ubiquitination were examined. An in vivo NSCLC xenograft model was used to corroborate the in vivo experimental results.
RESULTS: The study found an inverse correlation between FBXO33 expression in NSCLC and OS. Lower FBXO33 expression enhanced the growth, proliferation, migration, invasion, and
stemness characteristics of NSCLC cell lines. FBXO33 interacted with Myc to promote its ubiquitination and subsequent degradation, which suppressed NSCLC development.
CONCLUSIONS: FBXO33 is expressed at low levels in NSCLC and correlates with lower OS. Overexpression of FBXO33 promotes Myc ubiquitination and degradation and inhibits tumor cell proliferation, migration and
stemness characteristics, thereby impeding NSCLC progression.