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Cyclin-Dependent Kinase Inhibitor 3 Promotes Cancer Cell Proliferation and Tumorigenesis in Nasopharyngeal Carcinoma by Targeting p27

Nasopharyngeal carcinoma (NPC) is a common malignancy of the head and neck that arises from the nasopharynx epithelium and is highly invasive. Cyclin-dependent kinase inhibitor 3 (CDKN3) belongs to the dual-specificity protein phosphatase family, which plays a key role in regulating cell division. A...

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Autores principales: Wang, Huimin, Chen, Hexin, Zhou, Hang, Yu, Wenfa, Lu, Zhenmin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Cognizant Communication Corporation 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7840971/
https://www.ncbi.nlm.nih.gov/pubmed/28109073
http://dx.doi.org/10.3727/096504017X14835311718295
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author Wang, Huimin
Chen, Hexin
Zhou, Hang
Yu, Wenfa
Lu, Zhenmin
author_facet Wang, Huimin
Chen, Hexin
Zhou, Hang
Yu, Wenfa
Lu, Zhenmin
author_sort Wang, Huimin
collection PubMed
description Nasopharyngeal carcinoma (NPC) is a common malignancy of the head and neck that arises from the nasopharynx epithelium and is highly invasive. Cyclin-dependent kinase inhibitor 3 (CDKN3) belongs to the dual-specificity protein phosphatase family, which plays a key role in regulating cell division. Abnormal expression of CDKN3 has been found in numerous types of cancer. In the current study, we explored the possible role of CDKN3 in cell proliferation, ability to invade, and radiosensitivity in NPC cells. We reported that CDKN3 was upregulated and p27 was downregulated in NPC tissues and is associated with a worse prognosis for patients. In addition, downregulation of CDKN3 and upregulation of p27 decreased cell proliferation, induced cell cycle arrest, increased apoptosis, decreased cell invasion, and enhanced radiosensitivity. Silencing of p27 significantly inhibited the effects of the knockdown of CDKN3. Moreover, downregulation of CDKN3 and upregulation of p27 inhibited the increase in tumor volume and weight in implanted tumors, decreased the phosphorylation of Akt, and increased the expression of cleaved caspase 3 in tumors. CDKN3 expression was also inversely correlated with p27 expression in NPC patients. Knockdown of CDKN3 increased p27 expression. Silencing of p27 markedly inhibited the effects of CDKN3 on cell proliferation, cell cycle progression, apoptosis, invasion, and radiosensitivity. These results demonstrate that upregulation of p27 is involved in the knockdown of CDKN3-induced decrease in cell proliferation, increase in cell cycle arrest and apoptosis, decrease in invasion, and increase in radiosensitivity. The results demonstrate that the CDKN3/p27 axis may be a novel target in the treatment of NPC.
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spelling pubmed-78409712021-02-16 Cyclin-Dependent Kinase Inhibitor 3 Promotes Cancer Cell Proliferation and Tumorigenesis in Nasopharyngeal Carcinoma by Targeting p27 Wang, Huimin Chen, Hexin Zhou, Hang Yu, Wenfa Lu, Zhenmin Oncol Res Article Nasopharyngeal carcinoma (NPC) is a common malignancy of the head and neck that arises from the nasopharynx epithelium and is highly invasive. Cyclin-dependent kinase inhibitor 3 (CDKN3) belongs to the dual-specificity protein phosphatase family, which plays a key role in regulating cell division. Abnormal expression of CDKN3 has been found in numerous types of cancer. In the current study, we explored the possible role of CDKN3 in cell proliferation, ability to invade, and radiosensitivity in NPC cells. We reported that CDKN3 was upregulated and p27 was downregulated in NPC tissues and is associated with a worse prognosis for patients. In addition, downregulation of CDKN3 and upregulation of p27 decreased cell proliferation, induced cell cycle arrest, increased apoptosis, decreased cell invasion, and enhanced radiosensitivity. Silencing of p27 significantly inhibited the effects of the knockdown of CDKN3. Moreover, downregulation of CDKN3 and upregulation of p27 inhibited the increase in tumor volume and weight in implanted tumors, decreased the phosphorylation of Akt, and increased the expression of cleaved caspase 3 in tumors. CDKN3 expression was also inversely correlated with p27 expression in NPC patients. Knockdown of CDKN3 increased p27 expression. Silencing of p27 markedly inhibited the effects of CDKN3 on cell proliferation, cell cycle progression, apoptosis, invasion, and radiosensitivity. These results demonstrate that upregulation of p27 is involved in the knockdown of CDKN3-induced decrease in cell proliferation, increase in cell cycle arrest and apoptosis, decrease in invasion, and increase in radiosensitivity. The results demonstrate that the CDKN3/p27 axis may be a novel target in the treatment of NPC. Cognizant Communication Corporation 2017-11-02 /pmc/articles/PMC7840971/ /pubmed/28109073 http://dx.doi.org/10.3727/096504017X14835311718295 Text en Copyright © 2017 Cognizant, LLC. http://creativecommons.org/licenses/by-nc-nd/4.0/ This article is licensed under a Creative Commons Attribution-NonCommercial NoDerivatives 4.0 International License.
spellingShingle Article
Wang, Huimin
Chen, Hexin
Zhou, Hang
Yu, Wenfa
Lu, Zhenmin
Cyclin-Dependent Kinase Inhibitor 3 Promotes Cancer Cell Proliferation and Tumorigenesis in Nasopharyngeal Carcinoma by Targeting p27
title Cyclin-Dependent Kinase Inhibitor 3 Promotes Cancer Cell Proliferation and Tumorigenesis in Nasopharyngeal Carcinoma by Targeting p27
title_full Cyclin-Dependent Kinase Inhibitor 3 Promotes Cancer Cell Proliferation and Tumorigenesis in Nasopharyngeal Carcinoma by Targeting p27
title_fullStr Cyclin-Dependent Kinase Inhibitor 3 Promotes Cancer Cell Proliferation and Tumorigenesis in Nasopharyngeal Carcinoma by Targeting p27
title_full_unstemmed Cyclin-Dependent Kinase Inhibitor 3 Promotes Cancer Cell Proliferation and Tumorigenesis in Nasopharyngeal Carcinoma by Targeting p27
title_short Cyclin-Dependent Kinase Inhibitor 3 Promotes Cancer Cell Proliferation and Tumorigenesis in Nasopharyngeal Carcinoma by Targeting p27
title_sort cyclin-dependent kinase inhibitor 3 promotes cancer cell proliferation and tumorigenesis in nasopharyngeal carcinoma by targeting p27
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7840971/
https://www.ncbi.nlm.nih.gov/pubmed/28109073
http://dx.doi.org/10.3727/096504017X14835311718295
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