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泛素 E3 连接酶 FBXO33 通过促进 Myc 的泛素化和降解来抑制非小细胞肺癌中的干细胞样特性和转移。

The Ubiquitin E3 Ligase FBXO33 Suppresses Stem Cell-Like Properties and Metastasis in Non-Small-Cell Lung Cancer by Promoting Ubiquitination and Degradation of Myc.

机构信息

Department of Oncology, The Second Affiliated Hospital of Nanjing Medical University, 210000 Nanjing, Jiangsu, China.

Department of Respiratory and Critical Care Medicine, Affiliated Hospital 2 of Nantong University, 226001 Nantong, Jiangsu, China.

出版信息

Front Biosci (Landmark Ed). 2024 Aug 21;29(8):296. doi: 10.31083/j.fbl2908296.

DOI:10.31083/j.fbl2908296
PMID:39206900
Abstract

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 NSCLC xenograft model was used to corroborate the 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.

CONCLUSION

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.

摘要

背景

非小细胞肺癌(NSCLC)是一种恶性肺癌,通过确定关键治疗靶点可以改善其预后。因此,本研究探讨了 F-box 仅蛋白 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 NSCLC 中 FBXO33 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。通过定量聚合酶链反应(qPCR)、western blot(WB)和免疫荧光(IF)验证这些结果。通过过表达或敲低调节 FBXO33 表达,并分析其对 NSCLC 细胞系中细胞生长、增殖、迁移、侵袭和干性特征的影响。此外,还研究了 FBXO33 与髓细胞瘤(Myc)之间的相互作用及其对 Myc 泛素化的影响。使用 NSCLC 异种移植模型来证实实验结果。

结果

研究发现 FBXO33 在 NSCLC 中的表达与 OS 呈负相关。较低的 FBXO33 表达增强了 NSCLC 细胞系的生长、增殖、迁移、侵袭和干性特征。FBXO33 与 Myc 相互作用,促进其泛素化和随后的降解,从而抑制 NSCLC 的发展。

结论

FBXO33 在 NSCLC 中表达水平较低,与较低的 OS 相关。FBXO33 的过表达促进 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 的进展。

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