USP5 knockdown alleviates lung cancer progression via activating PARP1-mediated mTOR signaling pathway
Lei Cao1, Hongsheng Liu1, Cheng Huang1
1Department of Thoracic Surgery, Peking Union Medical College, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, No. 1, Shuai Fu Yuan, Dong Cheng District, Beijing, 100730, China.
Background:
With the rapidly increasing morbidity and mortality, lung cancer has been considered one of the serious malignant tumors, affecting millions of patients globally. Currently, the pathogenesis of lung cancer remains unclear, hindering the development of effective treatment. This study aims to investigate the mechanisms of lung cancer and develop an effective therapeutic approach for intervention in preventing lung cancer progress.
Methods:
The USP5 levels are detected in lung cancerous and paracancerous tissue by quantitative real-time polymerase chain reaction (qRT-PCR) and Western blotting methods to explore their roles in lung cancer progression. MTT, colony assay, and transwell chamber approaches are employed to measure cell viability, proliferation, and migration, respectively. Further, flow cytometry experiments are performed to examine the effect of USP5 on lung cancer. Finally, the investigations in vivo are executed using the mice subcutaneous tumor model to identify the effect of USP5 in promoting lung cancer development.
Results:
Notably, USP5 is highly expressed in lung cancer, USP5 overexpression promoted the proliferation and migration in the lung cancer cell lines, H1299 and A549, while knockdown of USP5 inhibited these via regulating the PARP1-mediated mTOR signaling pathway. Furthermore, the subcutaneous tumors model was established in C57BL/6 mice, and the volume of subcutaneous tumors was significantly reduced after silencing USP5, while increased after USP5 overexpression and decreased significantly with shRARP1 treatment at the same time.
Conclusions:
Together, USP5 could promote the progression of lung cancer cells by mTOR signaling pathway and interacting with PARP1, indicating that USP5 may become a new target for lung cancer treatment.
Insights
The study found that USP5 promotes lung cancer progression by regulating the PARP1-mediated mTOR signaling pathway. Silencing USP5 inhibited tumor growth, suggesting USP5 as a potential therapeutic target for lung cancer.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- Lung cancer presents a significant global health challenge with high morbidity and mortality.
- The precise mechanisms driving lung cancer pathogenesis remain largely unknown, impeding effective treatment development.
- Understanding these mechanisms is crucial for developing novel therapeutic strategies.
Purpose of the Study:
- To investigate the role of USP family member 5 (USP5) in lung cancer progression.
- To elucidate the molecular mechanisms by which USP5 influences lung cancer development.
- To evaluate USP5 as a potential therapeutic target for lung cancer intervention.
Main Methods:
- Quantitative real-time polymerase chain reaction (qRT-PCR) and Western blotting to assess USP5 expression in lung tissues.
- In vitro assays (MTT, colony formation, Transwell) to evaluate the impact of USP5 on cancer cell viability, proliferation, and migration.
- Flow cytometry to analyze USP5's effects on lung cancer cells.
- In vivo studies using a mouse subcutaneous tumor model to assess USP5's role in tumor growth.
Main Results:
- USP5 is highly expressed in lung cancer tissues.
- USP5 overexpression enhanced proliferation and migration in lung cancer cell lines (H1299, A549).
- USP5 knockdown inhibited these processes by regulating the PARP1-mediated mTOR signaling pathway.
- In vivo, USP5 silencing reduced tumor volume, while overexpression increased it; shRARP1 treatment significantly decreased tumor volume.
Conclusions:
- USP5 promotes lung cancer progression through the mTOR signaling pathway by interacting with PARP1.
- USP5 represents a promising novel therapeutic target for the treatment of lung cancer.
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