Ubiquitin specific peptidase 49 inhibits non‐small cell lung cancer cell growth by suppressing PI3K/AKT signaling

Autor: Rui‐Jun Xu, Wen‐Ming Shen, Da‐Fu Xu, Jin‐Nan Yin, Shi‐Ying Zheng
Rok vydání: 2019
Předmět:
non‐small cell lung cancer
PTEN
Lung Neoplasms
Cell cycle checkpoint
USP49
Resting Phase
Cell Cycle
Flow cytometry
Phosphatidylinositol 3-Kinases
03 medical and health sciences
0302 clinical medicine
Cyclin D1
Carcinoma
Non-Small-Cell Lung
Cell Line
Tumor
medicine
Humans
RNA
Small Interfering
Lung
Protein kinase B
PI3K/AKT/mTOR pathway
Cell Proliferation
lcsh:R5-920
medicine.diagnostic_test
biology
Cell growth
business.industry
AKT
PTEN Phosphohydrolase
Cell Cycle Checkpoints
General Medicine
Survival Analysis
respiratory tract diseases
Gene Expression Regulation
Neoplastic
HEK293 Cells
Cell culture
030220 oncology & carcinogenesis
Cancer research
biology.protein
Deubiquitination
030211 gastroenterology & hepatology
Tumor Suppressor Protein p53
lcsh:Medicine (General)
business
Proto-Oncogene Proteins c-akt
Ubiquitin Thiolesterase
Signal Transduction
Zdroj: Kaohsiung Journal of Medical Sciences, Vol 35, Iss 7, Pp 401-407 (2019)
ISSN: 2410-8650
1607-551X
DOI: 10.1002/kjm2.12073
Popis: Ubiquitin specific peptidase 49 (USP49) has been reported as a tumor suppressor in several tumors, but its function and molecular mechanism in non‐small cell lung cancer (NSCLC) are still unknown. In this study, USP49 was found downregulated in NSCLC primary tissues and cell lines, and high USP49 predicted a positive index for the overall survival of NSCLC patients. Overexpression of USP49 downregulated the expression levels of Cyclin D1, and upregulated p53 expression. Further flow cytometry analysis showed that overexpressed USP49 induced cell cycle arrest at G0/G1 phase. As a result, overexpression of USP49 significantly inhibited cell growth of NSCLC cells. In mechanism, overexpression of USP49 inhibited PI3K/AKT signaling, but knockdown of USP49 enhanced this signaling. Further studies indicated that USP49 deubiquitinated PTEN and stabilized PTEN protein, which suggested that USP49 inhibited PI3K/AKT signaling by stabilizing PTEN in NSCLC cells. In conclusion, we demonstrated that USP49 was functional in NSCLC cells, and inhibited NSCLC cell growth by suppressing PI3K/AKT signaling, suggesting that USP49 could be as a novel target for NSCLC therapy.
Databáze: OpenAIRE
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