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Downregulation of PAX6 by shRNA Inhibits Proliferation and Cell Cycle Progression of Human Non-Small Cell Lung Cancer Cell Lines

BACKGROUND: The transcription factor PAX6 is primarily expressed in embryos. PAX6 is also expressed in several tumors and plays an oncogenic role. However, little is known about the role of PAX6 in lung cancer. METHODS: The function of PAX6 in lung cancer cells was evaluated by small interfering RNA...

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Autores principales: Zhao, Xiaoting, Yue, Wentao, Zhang, Lina, Ma, Li, Jia, Wenyun, Qian, Zhe, Zhang, Chunyan, Wang, Yue
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3893268/
https://www.ncbi.nlm.nih.gov/pubmed/24454925
http://dx.doi.org/10.1371/journal.pone.0085738
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author Zhao, Xiaoting
Yue, Wentao
Zhang, Lina
Ma, Li
Jia, Wenyun
Qian, Zhe
Zhang, Chunyan
Wang, Yue
author_facet Zhao, Xiaoting
Yue, Wentao
Zhang, Lina
Ma, Li
Jia, Wenyun
Qian, Zhe
Zhang, Chunyan
Wang, Yue
author_sort Zhao, Xiaoting
collection PubMed
description BACKGROUND: The transcription factor PAX6 is primarily expressed in embryos. PAX6 is also expressed in several tumors and plays an oncogenic role. However, little is known about the role of PAX6 in lung cancer. METHODS: The function of PAX6 in lung cancer cells was evaluated by small interfering RNA-mediated depletion of the protein followed by analyses of cell proliferation, anchorage-independent growth, and cell cycle arrest. The changes of cyclin D1, pRB, ERK1/2, p38 expression caused by PAX6 inhibition were detected using western-blotting. The PAX6 mRNA level in 52 pairs of tumors and corresponding matched adjacent normal tissues from non-small cell lung cancer patients and lung cancer cell lines was detected by real-time PCR. RESULTS: Suppression of PAX6 expression inhibited cell growth and colony formation in A549 and H1299 cells. The percentage of cells in G1-phase increased when PAX6 expression was inhibited. The cyclin D1 protein level, as well as the pRB phosphorylation level, decreased as a result of PAX6 down-regulation. The activity of ERK1/2 and p38 was also suppressed in PAX6 knock-down cells. The PAX6 mRNA was highly expressed in lung cancer tissue and lung cancer cell lines. In most patients (about 65%), the relative ratio of PAX6 mRNA in primary NSCLC versus adjacent tissues exceeded 100. CONCLUSIONS: Our data implicated that PAX6 accelerates cell cycle progression by activating MAPK signal pathway. PAX6 mRNA levels were significantly elevated in primary lung cancer tissues compared to their matched adjacent tissues.
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spelling pubmed-38932682014-01-21 Downregulation of PAX6 by shRNA Inhibits Proliferation and Cell Cycle Progression of Human Non-Small Cell Lung Cancer Cell Lines Zhao, Xiaoting Yue, Wentao Zhang, Lina Ma, Li Jia, Wenyun Qian, Zhe Zhang, Chunyan Wang, Yue PLoS One Research Article BACKGROUND: The transcription factor PAX6 is primarily expressed in embryos. PAX6 is also expressed in several tumors and plays an oncogenic role. However, little is known about the role of PAX6 in lung cancer. METHODS: The function of PAX6 in lung cancer cells was evaluated by small interfering RNA-mediated depletion of the protein followed by analyses of cell proliferation, anchorage-independent growth, and cell cycle arrest. The changes of cyclin D1, pRB, ERK1/2, p38 expression caused by PAX6 inhibition were detected using western-blotting. The PAX6 mRNA level in 52 pairs of tumors and corresponding matched adjacent normal tissues from non-small cell lung cancer patients and lung cancer cell lines was detected by real-time PCR. RESULTS: Suppression of PAX6 expression inhibited cell growth and colony formation in A549 and H1299 cells. The percentage of cells in G1-phase increased when PAX6 expression was inhibited. The cyclin D1 protein level, as well as the pRB phosphorylation level, decreased as a result of PAX6 down-regulation. The activity of ERK1/2 and p38 was also suppressed in PAX6 knock-down cells. The PAX6 mRNA was highly expressed in lung cancer tissue and lung cancer cell lines. In most patients (about 65%), the relative ratio of PAX6 mRNA in primary NSCLC versus adjacent tissues exceeded 100. CONCLUSIONS: Our data implicated that PAX6 accelerates cell cycle progression by activating MAPK signal pathway. PAX6 mRNA levels were significantly elevated in primary lung cancer tissues compared to their matched adjacent tissues. Public Library of Science 2014-01-15 /pmc/articles/PMC3893268/ /pubmed/24454925 http://dx.doi.org/10.1371/journal.pone.0085738 Text en © 2014 Zhao et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Zhao, Xiaoting
Yue, Wentao
Zhang, Lina
Ma, Li
Jia, Wenyun
Qian, Zhe
Zhang, Chunyan
Wang, Yue
Downregulation of PAX6 by shRNA Inhibits Proliferation and Cell Cycle Progression of Human Non-Small Cell Lung Cancer Cell Lines
title Downregulation of PAX6 by shRNA Inhibits Proliferation and Cell Cycle Progression of Human Non-Small Cell Lung Cancer Cell Lines
title_full Downregulation of PAX6 by shRNA Inhibits Proliferation and Cell Cycle Progression of Human Non-Small Cell Lung Cancer Cell Lines
title_fullStr Downregulation of PAX6 by shRNA Inhibits Proliferation and Cell Cycle Progression of Human Non-Small Cell Lung Cancer Cell Lines
title_full_unstemmed Downregulation of PAX6 by shRNA Inhibits Proliferation and Cell Cycle Progression of Human Non-Small Cell Lung Cancer Cell Lines
title_short Downregulation of PAX6 by shRNA Inhibits Proliferation and Cell Cycle Progression of Human Non-Small Cell Lung Cancer Cell Lines
title_sort downregulation of pax6 by shrna inhibits proliferation and cell cycle progression of human non-small cell lung cancer cell lines
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3893268/
https://www.ncbi.nlm.nih.gov/pubmed/24454925
http://dx.doi.org/10.1371/journal.pone.0085738
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