Ubiquitin‐specific protease 44 inhibits cell growth by suppressing AKT signaling in non‐small cell lung cancer
Abstract Ubiquitin‐specific protease 44 (USP44) has been reported as a tumor suppressor or promoter in some tumors, but its function in non‐small cell lung cancer (NSCLC) is still unclear. In this study, USP44 was found significantly downregulated in both of NSCLC tissues and cell lines, and low exp...
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doaj-af93a7269f304f758b38aa1bf2e444872020-11-24T21:59:44ZengWileyKaohsiung Journal of Medical Sciences1607-551X2410-86502019-09-0135953554110.1002/kjm2.12096Ubiquitin‐specific protease 44 inhibits cell growth by suppressing AKT signaling in non‐small cell lung cancerYun‐Kui Zhang0Wen‐Ze Tian1Rong‐Sheng Zhang2Yu‐Jie Zhang3Hai‐Tao Ma4Department of Thoracic Surgery The First Affiliated Hospital of Soochow University Suzhou ChinaDepartment of Thoracic Surgery Huai'an First People's Hospital, The Affiliated Huai'an No. 1 People's Hospital of Nanjing Medical University Huai'an Jiangsu ChinaDepartment of Thoracic Surgery Shanxi Tumor Hospital Taiyuan ChinaDepartment of Thoracic Surgery Shanxi Tumor Hospital Taiyuan ChinaDepartment of Thoracic Surgery The First Affiliated Hospital of Soochow University Suzhou ChinaAbstract Ubiquitin‐specific protease 44 (USP44) has been reported as a tumor suppressor or promoter in some tumors, but its function in non‐small cell lung cancer (NSCLC) is still unclear. In this study, USP44 was found significantly downregulated in both of NSCLC tissues and cell lines, and low expression of USP44 predicted a poor prognosis for NSCLC patients. Overexpression of USP44 markedly downregulated the expression levels of Cyclin D1 and CDK4, but upregulated p53 expression, as a result of which, suppressing the cell growth of NSCLC cells. Further studies indicated that overexpression of USP44 significantly inhibited the phosphorylation of AKT, and its down‐stream signals, including mTOR and P70S6K. Moreover, overexpression of USP44 increased PTEN protein but not its mRNA levels, which suggested that USP44 inhibited AKT signaling by stabilizing PTEN in NSCLC cells. In conclusion, we demonstrated that USP44 showed prior evidence of a tumor suppressive function in NSCLC cells, and inhibited NSCLC cell growth by suppressing AKT signaling, suggesting that USP44 could be as a novel target for NSCLC therapy.https://doi.org/10.1002/kjm2.12096AKTDeubiquitinaseNSCLCPTENUSP44 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Yun‐Kui Zhang Wen‐Ze Tian Rong‐Sheng Zhang Yu‐Jie Zhang Hai‐Tao Ma |
spellingShingle |
Yun‐Kui Zhang Wen‐Ze Tian Rong‐Sheng Zhang Yu‐Jie Zhang Hai‐Tao Ma Ubiquitin‐specific protease 44 inhibits cell growth by suppressing AKT signaling in non‐small cell lung cancer Kaohsiung Journal of Medical Sciences AKT Deubiquitinase NSCLC PTEN USP44 |
author_facet |
Yun‐Kui Zhang Wen‐Ze Tian Rong‐Sheng Zhang Yu‐Jie Zhang Hai‐Tao Ma |
author_sort |
Yun‐Kui Zhang |
title |
Ubiquitin‐specific protease 44 inhibits cell growth by suppressing AKT signaling in non‐small cell lung cancer |
title_short |
Ubiquitin‐specific protease 44 inhibits cell growth by suppressing AKT signaling in non‐small cell lung cancer |
title_full |
Ubiquitin‐specific protease 44 inhibits cell growth by suppressing AKT signaling in non‐small cell lung cancer |
title_fullStr |
Ubiquitin‐specific protease 44 inhibits cell growth by suppressing AKT signaling in non‐small cell lung cancer |
title_full_unstemmed |
Ubiquitin‐specific protease 44 inhibits cell growth by suppressing AKT signaling in non‐small cell lung cancer |
title_sort |
ubiquitin‐specific protease 44 inhibits cell growth by suppressing akt signaling in non‐small cell lung cancer |
publisher |
Wiley |
series |
Kaohsiung Journal of Medical Sciences |
issn |
1607-551X 2410-8650 |
publishDate |
2019-09-01 |
description |
Abstract Ubiquitin‐specific protease 44 (USP44) has been reported as a tumor suppressor or promoter in some tumors, but its function in non‐small cell lung cancer (NSCLC) is still unclear. In this study, USP44 was found significantly downregulated in both of NSCLC tissues and cell lines, and low expression of USP44 predicted a poor prognosis for NSCLC patients. Overexpression of USP44 markedly downregulated the expression levels of Cyclin D1 and CDK4, but upregulated p53 expression, as a result of which, suppressing the cell growth of NSCLC cells. Further studies indicated that overexpression of USP44 significantly inhibited the phosphorylation of AKT, and its down‐stream signals, including mTOR and P70S6K. Moreover, overexpression of USP44 increased PTEN protein but not its mRNA levels, which suggested that USP44 inhibited AKT signaling by stabilizing PTEN in NSCLC cells. In conclusion, we demonstrated that USP44 showed prior evidence of a tumor suppressive function in NSCLC cells, and inhibited NSCLC cell growth by suppressing AKT signaling, suggesting that USP44 could be as a novel target for NSCLC therapy. |
topic |
AKT Deubiquitinase NSCLC PTEN USP44 |
url |
https://doi.org/10.1002/kjm2.12096 |
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