Rab5if is a potential therapeutic target of NSCLC
Linjuan Lu1, Lixiu Chen1, Feng Gao1
1Department of Respiratory and Critical Care Medicine, The Affiliated Zhangjiagang Hospital of Soochow University, Suzhou, China.
Purpose:
Due to disease progression and drug resistance, non-small cell lung cancer(NSCLC) mortality remains high, and the study of new targets that can inhibit tumor growth is very necessary. The purpose of this study was to investigate the role of Rab5if in the occurrence and development of NSCLC and explore its potential role in the treatment of NSCLC.
Materials And Methods:
Rab5if overexpression and knockdown non-small cell lung cancer cell lines were constructed by lentivirus. Cellular assays were conducted to assess the impact of Rab5if on the functionality of lung cancer cells, The mechanism by which Rab5if influences the function of lung cancer cells was confirmed through Western blot analysis. The in vivo experiment was used to further verify the results of the in vitro experiment.
Results:
Bioinformatics research found Rab5if mRNA increased in patients with NSCLC. Increased mRNA and protein levels of Rab5if were confirmed in local human NSCLC tissues. Knockdown of Rab5if in NSCLC cell lines by lentivirus significantly inhibited cell vigour, propagation and migration. In addition, mitochondrial function was impaired in lung cancer cells after Rab5if knockdown. In contrast, Rab5if overexpression promoted the proliferation and migration of NSCLC. Moreover, the impact Rab5if on the function of lung cancer cells was realized through the AKT-mTOR pathway. In the in vivo study, growth inhibition were observed in lung cancer xenografts transfected with Rab5if shRNA in nude mice. Similarly, xenografts of nude mice overexpressing Rab5if grew rapidly. The same pathway as in vitro was confirmed in vivo.
Conclusion:
Rab5if is expected to be a novel therapeutic target for NSCLC.
Insights
Rab5if promotes non-small cell lung cancer (NSCLC) growth and migration. Targeting Rab5if may offer a new therapeutic strategy for NSCLC, as inhibiting its expression reduced tumor progression in vitro and in vivo.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- Non-small cell lung cancer (NSCLC) remains a leading cause of cancer mortality globally.
- High mortality rates are attributed to disease progression and acquired drug resistance.
- Novel therapeutic targets are crucial for improving NSCLC treatment outcomes.
Purpose of the Study:
- To investigate the role of Rab5if in the development and progression of NSCLC.
- To explore the potential of Rab5if as a therapeutic target for NSCLC treatment.
Main Methods:
- Construction of Rab5if-overexpressing and knockdown NSCLC cell lines using lentivirus.
- In vitro cellular assays to assess proliferation, migration, and mitochondrial function.
- Western blot analysis to elucidate the underlying molecular mechanisms.
- In vivo xenograft studies in nude mice to validate in vitro findings.
Main Results:
- Rab5if mRNA and protein levels were elevated in NSCLC tissues and cell lines.
- Rab5if knockdown significantly inhibited NSCLC cell proliferation, migration, and mitochondrial function.
- Rab5if overexpression promoted NSCLC cell proliferation and migration.
- The AKT-mTOR pathway was identified as the key mechanism mediating Rab5if's effects.
- In vivo studies confirmed that Rab5if knockdown inhibited tumor growth, while overexpression accelerated it.
Conclusions:
- Rab5if plays a significant role in NSCLC progression.
- Rab5if is a potential novel therapeutic target for NSCLC treatment.
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