KEY TAKEAWAYS
- The study aimed to investigate how FBXO33 suppresses NSCLC progression by targeting Myc for degradation.
- Researchers noticed that FBXO33 overexpression inhibits NSCLC progression by promoting Myc degradation and reducing tumor cell proliferation and migration.
Non-small cell lung cancer (NSCLC) is an aggressive type of lung cancer with limited therapeutic options and poor prognosis. Identifying key therapeutic targets could significantly enhance treatment outcomes.
Qiong Wei and the team aimed to explore the potential role of F-box Only Protein 33 (FBXO33) in NSCLC, focusing on its impact on tumor progression and associated mechanisms.
They performed an inclusive analysis of FBXO33 expression levels in NSCLC using the University of Alabama at Birmingham Cancer Data Analysis Portal (UALCAN), and correlated these levels with overall survival (OS) through Kaplan-Meier survival analysis. Validation was achieved through quantitative polymerase chain reaction (qPCR), western blot (WB), and immunofluorescence (IF).
The study involved modulating FBXO33 expression in NSCLC cell lines through overexpression or knockdown and assessed its effects on cell growth, proliferation, migration, invasion, and stemness characteristics. Additionally, the interaction between FBXO33 and Myelocytomatosis (Myc) and its impact on Myc ubiquitination were investigated. An in vivo NSCLC xenograft model was used to confirm the experimental results observed in cell lines.
The results showed that, an inverse correlation was observed between FBXO33 expression in NSCLC and OS. Reduced FBXO33 levels were associated with increased growth, proliferation, migration, invasion, and stemness characteristics in NSCLC cell lines. FBXO33 was found to interact with Myc, facilitating its ubiquitination and subsequent degradation, which effectively suppressed NSCLC development.
The study concluded that low levels of FBXO33 expression in NSCLC are associated with poorer OS. It was found that increasing FBXO33 levels enhances Myc ubiquitination and degradation, leading to reduced tumor cell proliferation, migration, and stemness, which helps to hinder the progression of NSCLC.
The study is funded by the National Natural Science Foundation of China, QA2021012/ Project of Nantong Municipal Health Commission.
Source: https://pubmed.ncbi.nlm.nih.gov/39206900/
Wei Q, Liu Z, Zhu J, et al. (2024). “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.” Front Biosci (Landmark Ed). 2024;29(8):296. doi:10.31083/j.fbl2908296
