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Knocking down USP39 Inhibits the Growth and Metastasis of Non-Small-Cell Lung Cancer Cells through Activating the p53 Pathway

Ubiquitin-specific protease 39 (USP39), a member of the deubiquitinating enzyme family, has been reported to participate in cytokinesis and metastasis. Previous studies determined that USP39 functions as an oncogenic factor in various types of cancer. Here, we reported that USP39 is frequently overe...

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Autores principales: Yuan, Jiahui, Zhang, Gongye, Li, Xiaomei, Ma, Qiujuan, Cheng, Weipeng, Wang, Weiwei, Zhang, Bing, Hu, Tianhui, Song, Gang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7728369/
https://www.ncbi.nlm.nih.gov/pubmed/33255748
http://dx.doi.org/10.3390/ijms21238949
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author Yuan, Jiahui
Zhang, Gongye
Li, Xiaomei
Ma, Qiujuan
Cheng, Weipeng
Wang, Weiwei
Zhang, Bing
Hu, Tianhui
Song, Gang
author_facet Yuan, Jiahui
Zhang, Gongye
Li, Xiaomei
Ma, Qiujuan
Cheng, Weipeng
Wang, Weiwei
Zhang, Bing
Hu, Tianhui
Song, Gang
author_sort Yuan, Jiahui
collection PubMed
description Ubiquitin-specific protease 39 (USP39), a member of the deubiquitinating enzyme family, has been reported to participate in cytokinesis and metastasis. Previous studies determined that USP39 functions as an oncogenic factor in various types of cancer. Here, we reported that USP39 is frequently overexpressed in human lung cancer tissues and non-small-cell lung cancer (NSCLC) cell lines. USP39 knockdown inhibited the proliferation and colony formation of A549 and HCC827 cells and decreased tumorigenic potential in nude mice. Specifically, knocking down USP39 resulted in cell cycle arrest at G2/M and subsequent apoptosis through the activation of the p53 pathway, including upregulation of p21, cleaved-cas3, cleaved-cas9 and downregulation of CDC2 and CycinB1. Moreover, USP39 knockdown significantly inhibited migration and invasion of A549 and HCC827 cells, also via activation of the p53 pathway, and downregulation of MMP2 and MMP9. Importantly, we verified these results in metastasis models in vivo. Collectively, these results not only establish that USP39 functions as an oncogene in lung cancer, but reveal that USP39 has an essential role in regulating cell proliferation and metastasis via activation of the p53 pathway.
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spelling pubmed-77283692020-12-11 Knocking down USP39 Inhibits the Growth and Metastasis of Non-Small-Cell Lung Cancer Cells through Activating the p53 Pathway Yuan, Jiahui Zhang, Gongye Li, Xiaomei Ma, Qiujuan Cheng, Weipeng Wang, Weiwei Zhang, Bing Hu, Tianhui Song, Gang Int J Mol Sci Article Ubiquitin-specific protease 39 (USP39), a member of the deubiquitinating enzyme family, has been reported to participate in cytokinesis and metastasis. Previous studies determined that USP39 functions as an oncogenic factor in various types of cancer. Here, we reported that USP39 is frequently overexpressed in human lung cancer tissues and non-small-cell lung cancer (NSCLC) cell lines. USP39 knockdown inhibited the proliferation and colony formation of A549 and HCC827 cells and decreased tumorigenic potential in nude mice. Specifically, knocking down USP39 resulted in cell cycle arrest at G2/M and subsequent apoptosis through the activation of the p53 pathway, including upregulation of p21, cleaved-cas3, cleaved-cas9 and downregulation of CDC2 and CycinB1. Moreover, USP39 knockdown significantly inhibited migration and invasion of A549 and HCC827 cells, also via activation of the p53 pathway, and downregulation of MMP2 and MMP9. Importantly, we verified these results in metastasis models in vivo. Collectively, these results not only establish that USP39 functions as an oncogene in lung cancer, but reveal that USP39 has an essential role in regulating cell proliferation and metastasis via activation of the p53 pathway. MDPI 2020-11-25 /pmc/articles/PMC7728369/ /pubmed/33255748 http://dx.doi.org/10.3390/ijms21238949 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Yuan, Jiahui
Zhang, Gongye
Li, Xiaomei
Ma, Qiujuan
Cheng, Weipeng
Wang, Weiwei
Zhang, Bing
Hu, Tianhui
Song, Gang
Knocking down USP39 Inhibits the Growth and Metastasis of Non-Small-Cell Lung Cancer Cells through Activating the p53 Pathway
title Knocking down USP39 Inhibits the Growth and Metastasis of Non-Small-Cell Lung Cancer Cells through Activating the p53 Pathway
title_full Knocking down USP39 Inhibits the Growth and Metastasis of Non-Small-Cell Lung Cancer Cells through Activating the p53 Pathway
title_fullStr Knocking down USP39 Inhibits the Growth and Metastasis of Non-Small-Cell Lung Cancer Cells through Activating the p53 Pathway
title_full_unstemmed Knocking down USP39 Inhibits the Growth and Metastasis of Non-Small-Cell Lung Cancer Cells through Activating the p53 Pathway
title_short Knocking down USP39 Inhibits the Growth and Metastasis of Non-Small-Cell Lung Cancer Cells through Activating the p53 Pathway
title_sort knocking down usp39 inhibits the growth and metastasis of non-small-cell lung cancer cells through activating the p53 pathway
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7728369/
https://www.ncbi.nlm.nih.gov/pubmed/33255748
http://dx.doi.org/10.3390/ijms21238949
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