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Yeast As a Chassis for Developing Functional Assays to Study Human P53
Published on: August 4, 2019
USP22 promotes NSCLC tumorigenesis via MDMX up-regulation and subsequent p53 inhibition
Fangbao Ding1, Chunrong Bao2, Yue Tian3
1Department of Cardiothoracic Surgery, Xinhua Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai 200092, China. drnail@sina.com.
Abstract:
Increasing evidence suggests that ubiquitin-specific protease 22 (USP22) has great clinicopathologic significance in oncology. In this study, we investigated the role of USP22 in human NSCLC tumorigenesis along with the underlying mechanisms of action. First, we determined the expression of USP22 in human NSCLC, as well as normal tissues and cell lines. We then studied the effects of USP22 silencing by shRNA on NSCLC cell growth in vitro and tumorigenesis in vivo, along with the effect on the p53 pathway. We found that USP22 is overexpressed in human NSCLC tissues and cell lines. USP22 silencing by shRNA inhibits proliferation, induces apoptosis and arrests cells at the G0/G1 phases in NSCLC cells and curbs human NSCLC tumor growth in a mouse xenograft model. Additionally, USP22 silencing downregulates MDMX protein expression and activates the p53 pathway. Our co-immunoprecipitation analysis shows that USP22 interacts with MDMX in NSCLC cells. Furthermore, MDMX silencing leads to growth arrest and apoptosis in NSCLC cells, and over-expression of MDMX reverses the USP22 silencing-induced effects. Taken together, our results suggest that USP22 promotes NSCLC tumorigenesis in vitro and in vivo through MDMX upregulation and subsequent p53 inhibition. USP22 may represent a novel target for NSCLC treatment.
Insights
Ubiquitin-specific protease 22 (USP22) promotes non-small cell lung cancer (NSCLC) growth by upregulating MDMX and inhibiting p53. Silencing USP22 offers a potential therapeutic strategy for NSCLC.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- Ubiquitin-specific protease 22 (USP22) is increasingly recognized for its significant role in cancer pathology.
- Understanding USP22's function in non-small cell lung cancer (NSCLC) is crucial for developing targeted therapies.
Purpose of the Study:
- To investigate the role of USP22 in human NSCLC tumorigenesis.
- To elucidate the underlying molecular mechanisms involving the p53 pathway and MDMX.
Main Methods:
- Quantitative analysis of USP22 expression in NSCLC tissues and cell lines.
- USP22 silencing using short hairpin RNA (shRNA) in vitro and in vivo (mouse xenograft model).
- Assessment of cell proliferation, apoptosis, cell cycle, p53 pathway activation, and protein interactions (co-immunoprecipitation).
Main Results:
- USP22 is significantly overexpressed in NSCLC tissues and cell lines.
- USP22 silencing inhibited NSCLC cell proliferation, induced apoptosis, caused G0/G1 cell cycle arrest, and suppressed tumor growth.
- USP22 silencing downregulated MDMX, activated the p53 pathway, and USP22 was found to interact with MDMX.
Conclusions:
- USP22 promotes NSCLC tumorigenesis by upregulating MDMX and subsequently inhibiting the p53 pathway.
- USP22 represents a potential novel therapeutic target for non-small cell lung cancer treatment.
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