TAp63α Is Involved in Tobacco Smoke-Induced Lung Cancer EMT and the Anti-cancer Activity of Curcumin via miR-19 Transcriptional Suppression
As a key risk factor for lung cancer, tobacco smoke (TS) influences several cellular processes, including epithelial-mesenchymal transition (EMT). TAp63α is a crucial transcription factor involved in tumor progression. The present study was designed to investigate the potential role and underlying m...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2021-03-01
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| Series: | Frontiers in Cell and Developmental Biology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fcell.2021.645402/full |
| _version_ | 1818617571620945920 |
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| author | Chunfeng Xie Jianyun Zhu Jianyun Zhu Xue Yang Cong Huang Liping Zhou Zili Meng Xiaoting Li Caiyun Zhong Caiyun Zhong |
| author_facet | Chunfeng Xie Jianyun Zhu Jianyun Zhu Xue Yang Cong Huang Liping Zhou Zili Meng Xiaoting Li Caiyun Zhong Caiyun Zhong |
| author_sort | Chunfeng Xie |
| collection | DOAJ |
| description | As a key risk factor for lung cancer, tobacco smoke (TS) influences several cellular processes, including epithelial-mesenchymal transition (EMT). TAp63α is a crucial transcription factor involved in tumor progression. The present study was designed to investigate the potential role and underlying mechanisms of TAp63α in TS-induced lung cancer EMT. We found that compared to normal tissues, the tumor tissues collected from lung cancer patients showed a lower level of TAp63α expression, along with downregulated E-cadherin expression and upregulated Vimentin expression. Results of treatment with TAp63α and TAp63α siRNA as well as with tumor growth factor-β (TGF-β) showed that TAp63α acted as a tumor suppressor gene, and its upregulated expression suppressed lung cancer EMT. Significantly, TS exposure altered expression of EMT-related markers, enhanced cell migratory and invasive capacities, and decreased the TAp63α expression level in lung cancer cells. Overexpression of TAp63α significantly alleviated TS-stimulated lung cancer EMT. Mechanistically, TAp63α expression transcriptionally reduced the miR-19 level, which resulted in the suppression of lung cancer EMT. Additionally, as a natural compound possessing anti-cancer effects, curcumin inhibited TS-induced lung cancer EMT by increasing TAp63α expression and reducing miR-19 expression. Collectively, our results indicate that TAp63α inhibits TS-induced lung cancer EMT via transcriptionally suppressing miR-19 and the inhibitory effect of TAp63α on miR-19 mediates the anti-cancer action of curcumin. These findings provide new insights into novel targets for lung cancer prevention. |
| first_indexed | 2024-12-16T17:07:49Z |
| format | Article |
| id | doaj.art-777a8c5943714be79f4c30be924b9000 |
| institution | Directory Open Access Journal |
| issn | 2296-634X |
| language | English |
| last_indexed | 2024-12-16T17:07:49Z |
| publishDate | 2021-03-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Cell and Developmental Biology |
| spelling | doaj.art-777a8c5943714be79f4c30be924b90002022-12-21T22:23:31ZengFrontiers Media S.A.Frontiers in Cell and Developmental Biology2296-634X2021-03-01910.3389/fcell.2021.645402645402TAp63α Is Involved in Tobacco Smoke-Induced Lung Cancer EMT and the Anti-cancer Activity of Curcumin via miR-19 Transcriptional SuppressionChunfeng Xie0Jianyun Zhu1Jianyun Zhu2Xue Yang3Cong Huang4Liping Zhou5Zili Meng6Xiaoting Li7Caiyun Zhong8Caiyun Zhong9Department of Nutrition and Food Safety, School of Public Health, Nanjing Medical University, Nanjing, ChinaDepartment of Nutrition and Food Safety, School of Public Health, Nanjing Medical University, Nanjing, ChinaDepartment of Digestive Disease and Nutrition Research Center, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou, ChinaDepartment of Clinical Nutrition, Nanjing Drum Tower Hospital, Nanjing, ChinaGuangde Center for Diseases Prevention and Control, Guangde, ChinaCell Therapy Center, Xuanwu Hospital Capital Medical University, Beijing, ChinaDepartment of Respiratory Medicine, Huai’an First People’s Hospital, Nanjing Medical University, Huai’an, ChinaDepartment of Nutrition and Food Safety, School of Public Health, Nanjing Medical University, Nanjing, ChinaDepartment of Nutrition and Food Safety, School of Public Health, Nanjing Medical University, Nanjing, ChinaCenter for Global Health, School of Public Health, Nanjing Medical University, Nanjing, ChinaAs a key risk factor for lung cancer, tobacco smoke (TS) influences several cellular processes, including epithelial-mesenchymal transition (EMT). TAp63α is a crucial transcription factor involved in tumor progression. The present study was designed to investigate the potential role and underlying mechanisms of TAp63α in TS-induced lung cancer EMT. We found that compared to normal tissues, the tumor tissues collected from lung cancer patients showed a lower level of TAp63α expression, along with downregulated E-cadherin expression and upregulated Vimentin expression. Results of treatment with TAp63α and TAp63α siRNA as well as with tumor growth factor-β (TGF-β) showed that TAp63α acted as a tumor suppressor gene, and its upregulated expression suppressed lung cancer EMT. Significantly, TS exposure altered expression of EMT-related markers, enhanced cell migratory and invasive capacities, and decreased the TAp63α expression level in lung cancer cells. Overexpression of TAp63α significantly alleviated TS-stimulated lung cancer EMT. Mechanistically, TAp63α expression transcriptionally reduced the miR-19 level, which resulted in the suppression of lung cancer EMT. Additionally, as a natural compound possessing anti-cancer effects, curcumin inhibited TS-induced lung cancer EMT by increasing TAp63α expression and reducing miR-19 expression. Collectively, our results indicate that TAp63α inhibits TS-induced lung cancer EMT via transcriptionally suppressing miR-19 and the inhibitory effect of TAp63α on miR-19 mediates the anti-cancer action of curcumin. These findings provide new insights into novel targets for lung cancer prevention.https://www.frontiersin.org/articles/10.3389/fcell.2021.645402/fullTAp63αlung cancermiR-19EMTcurcumintobacco smoke |
| spellingShingle | Chunfeng Xie Jianyun Zhu Jianyun Zhu Xue Yang Cong Huang Liping Zhou Zili Meng Xiaoting Li Caiyun Zhong Caiyun Zhong TAp63α Is Involved in Tobacco Smoke-Induced Lung Cancer EMT and the Anti-cancer Activity of Curcumin via miR-19 Transcriptional Suppression Frontiers in Cell and Developmental Biology TAp63α lung cancer miR-19 EMT curcumin tobacco smoke |
| title | TAp63α Is Involved in Tobacco Smoke-Induced Lung Cancer EMT and the Anti-cancer Activity of Curcumin via miR-19 Transcriptional Suppression |
| title_full | TAp63α Is Involved in Tobacco Smoke-Induced Lung Cancer EMT and the Anti-cancer Activity of Curcumin via miR-19 Transcriptional Suppression |
| title_fullStr | TAp63α Is Involved in Tobacco Smoke-Induced Lung Cancer EMT and the Anti-cancer Activity of Curcumin via miR-19 Transcriptional Suppression |
| title_full_unstemmed | TAp63α Is Involved in Tobacco Smoke-Induced Lung Cancer EMT and the Anti-cancer Activity of Curcumin via miR-19 Transcriptional Suppression |
| title_short | TAp63α Is Involved in Tobacco Smoke-Induced Lung Cancer EMT and the Anti-cancer Activity of Curcumin via miR-19 Transcriptional Suppression |
| title_sort | tap63α is involved in tobacco smoke induced lung cancer emt and the anti cancer activity of curcumin via mir 19 transcriptional suppression |
| topic | TAp63α lung cancer miR-19 EMT curcumin tobacco smoke |
| url | https://www.frontiersin.org/articles/10.3389/fcell.2021.645402/full |
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