The Roles and Regulatory Mechanisms of Tight Junction Protein Cingulin and Transcription Factor Forkhead Box Protein O1 in Human Lung Adenocarcinoma A549 Cells and Normal Lung Epithelial Cells
Tight junction (TJ) protein cingulin (CGN) and transcription factor forkhead box protein O1 (FOXO1) contribute to the development of various cancers. Histone deacetylase (HDAC) inhibitors have a potential therapeutic role for some cancers. HDAC inhibitors affect the expression of both CGN and FOXO1....
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MDPI AG
2024-01-01
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| author | Daichi Ishii Yuma Shindo Wataru Arai Takumi Konno Takayuki Kohno Kazuya Honda Masahiro Miyajima Atsushi Watanabe Takashi Kojima |
| author_facet | Daichi Ishii Yuma Shindo Wataru Arai Takumi Konno Takayuki Kohno Kazuya Honda Masahiro Miyajima Atsushi Watanabe Takashi Kojima |
| author_sort | Daichi Ishii |
| collection | DOAJ |
| description | Tight junction (TJ) protein cingulin (CGN) and transcription factor forkhead box protein O1 (FOXO1) contribute to the development of various cancers. Histone deacetylase (HDAC) inhibitors have a potential therapeutic role for some cancers. HDAC inhibitors affect the expression of both CGN and FOXO1. However, the roles and regulatory mechanisms of CGN and FOXO1 are unknown in non-small cell lung cancer (NSCLC) and normal human lung epithelial (HLE) cells. In the present study, to investigate the effects of CGN and FOXO1 on the malignancy of NSCLC, we used A549 cells as human lung adenocarcinoma and primary human lung epithelial (HLE) cells as normal lung tissues and performed the knockdown of CGN and FOXO1 by siRNAs. Furthermore, to investigate the detailed mechanisms in the antitumor effects of HDAC inhibitors for NSCLC via CGN and FOXO1, A549 cells and HLE cells were treated with the HDAC inhibitors trichostatin A (TSA) and Quisinostat (JNJ-2648158). In A549 cells, the knockdown of CGN increased bicellular TJ protein claudin-2 (CLDN-2) via mitogen-activated protein kinase/adenosine monophosphate-activated protein kinase (MAPK/AMPK) pathways and induced cell migration, while the knockdown of FOXO1 increased claudin-4 (CLDN-4), decreased CGN, and induced cell proliferation. The knockdown of CGN and FOXO1 induced cell metabolism in A549 cells. TSA and Quisinostat increased CGN and tricellular TJ protein angulin-1/lipolysis-stimulated lipoprotein receptor (LSR) in A549. In normal HLE cells, the knockdown of CGN and FOXO1 increased CLDN-4, while HDAC inhibitors increased CGN and CLDN-4. In conclusion, the knockdown of CGN via FOXO1 contributes to the malignancy of NSCLC. Both HDAC inhibitors, TSA and Quisinostat, may have potential for use in therapy for lung adenocarcinoma via changes in the expression of CGN and FOXO1. |
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| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-08T03:57:00Z |
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| spelling | doaj.art-c019592da3d14f96a6159f723f7c69ab2024-02-09T15:13:09ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672024-01-01253141110.3390/ijms25031411The Roles and Regulatory Mechanisms of Tight Junction Protein Cingulin and Transcription Factor Forkhead Box Protein O1 in Human Lung Adenocarcinoma A549 Cells and Normal Lung Epithelial CellsDaichi Ishii0Yuma Shindo1Wataru Arai2Takumi Konno3Takayuki Kohno4Kazuya Honda5Masahiro Miyajima6Atsushi Watanabe7Takashi Kojima8Department of Thoracic Surgery, Sapporo Medical University School of Medicine, Sapporo 060-8556, JapanDepartment of Thoracic Surgery, Sapporo Medical University School of Medicine, Sapporo 060-8556, JapanDepartment of Thoracic Surgery, Sapporo Medical University School of Medicine, Sapporo 060-8556, JapanDepartment of Cell Science, Institute of Cancer Research, Sapporo Medical University School of Medicine, Sapporo 060-8556, JapanDepartment of Cell Science, Institute of Cancer Research, Sapporo Medical University School of Medicine, Sapporo 060-8556, JapanDepartment of Thoracic Surgery, Sapporo Medical University School of Medicine, Sapporo 060-8556, JapanDepartment of Thoracic Surgery, Sapporo Medical University School of Medicine, Sapporo 060-8556, JapanDepartment of Thoracic Surgery, Sapporo Medical University School of Medicine, Sapporo 060-8556, JapanDepartment of Cell Science, Institute of Cancer Research, Sapporo Medical University School of Medicine, Sapporo 060-8556, JapanTight junction (TJ) protein cingulin (CGN) and transcription factor forkhead box protein O1 (FOXO1) contribute to the development of various cancers. Histone deacetylase (HDAC) inhibitors have a potential therapeutic role for some cancers. HDAC inhibitors affect the expression of both CGN and FOXO1. However, the roles and regulatory mechanisms of CGN and FOXO1 are unknown in non-small cell lung cancer (NSCLC) and normal human lung epithelial (HLE) cells. In the present study, to investigate the effects of CGN and FOXO1 on the malignancy of NSCLC, we used A549 cells as human lung adenocarcinoma and primary human lung epithelial (HLE) cells as normal lung tissues and performed the knockdown of CGN and FOXO1 by siRNAs. Furthermore, to investigate the detailed mechanisms in the antitumor effects of HDAC inhibitors for NSCLC via CGN and FOXO1, A549 cells and HLE cells were treated with the HDAC inhibitors trichostatin A (TSA) and Quisinostat (JNJ-2648158). In A549 cells, the knockdown of CGN increased bicellular TJ protein claudin-2 (CLDN-2) via mitogen-activated protein kinase/adenosine monophosphate-activated protein kinase (MAPK/AMPK) pathways and induced cell migration, while the knockdown of FOXO1 increased claudin-4 (CLDN-4), decreased CGN, and induced cell proliferation. The knockdown of CGN and FOXO1 induced cell metabolism in A549 cells. TSA and Quisinostat increased CGN and tricellular TJ protein angulin-1/lipolysis-stimulated lipoprotein receptor (LSR) in A549. In normal HLE cells, the knockdown of CGN and FOXO1 increased CLDN-4, while HDAC inhibitors increased CGN and CLDN-4. In conclusion, the knockdown of CGN via FOXO1 contributes to the malignancy of NSCLC. Both HDAC inhibitors, TSA and Quisinostat, may have potential for use in therapy for lung adenocarcinoma via changes in the expression of CGN and FOXO1.https://www.mdpi.com/1422-0067/25/3/1411cingulin (CGN)forkhead box protein O1 (FOXO1)HDAC inhibitorangulin-1/LSRclaudin-2claudin-4 |
| spellingShingle | Daichi Ishii Yuma Shindo Wataru Arai Takumi Konno Takayuki Kohno Kazuya Honda Masahiro Miyajima Atsushi Watanabe Takashi Kojima The Roles and Regulatory Mechanisms of Tight Junction Protein Cingulin and Transcription Factor Forkhead Box Protein O1 in Human Lung Adenocarcinoma A549 Cells and Normal Lung Epithelial Cells International Journal of Molecular Sciences cingulin (CGN) forkhead box protein O1 (FOXO1) HDAC inhibitor angulin-1/LSR claudin-2 claudin-4 |
| title | The Roles and Regulatory Mechanisms of Tight Junction Protein Cingulin and Transcription Factor Forkhead Box Protein O1 in Human Lung Adenocarcinoma A549 Cells and Normal Lung Epithelial Cells |
| title_full | The Roles and Regulatory Mechanisms of Tight Junction Protein Cingulin and Transcription Factor Forkhead Box Protein O1 in Human Lung Adenocarcinoma A549 Cells and Normal Lung Epithelial Cells |
| title_fullStr | The Roles and Regulatory Mechanisms of Tight Junction Protein Cingulin and Transcription Factor Forkhead Box Protein O1 in Human Lung Adenocarcinoma A549 Cells and Normal Lung Epithelial Cells |
| title_full_unstemmed | The Roles and Regulatory Mechanisms of Tight Junction Protein Cingulin and Transcription Factor Forkhead Box Protein O1 in Human Lung Adenocarcinoma A549 Cells and Normal Lung Epithelial Cells |
| title_short | The Roles and Regulatory Mechanisms of Tight Junction Protein Cingulin and Transcription Factor Forkhead Box Protein O1 in Human Lung Adenocarcinoma A549 Cells and Normal Lung Epithelial Cells |
| title_sort | roles and regulatory mechanisms of tight junction protein cingulin and transcription factor forkhead box protein o1 in human lung adenocarcinoma a549 cells and normal lung epithelial cells |
| topic | cingulin (CGN) forkhead box protein O1 (FOXO1) HDAC inhibitor angulin-1/LSR claudin-2 claudin-4 |
| url | https://www.mdpi.com/1422-0067/25/3/1411 |
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