Smoking behavior associated upregulation of SERPINB12 promotes proliferation and metastasis via activating WNT signaling in NSCLC
Abstract Background Non-small cell lung cancer (NSCLC) is the leading cause of morality among all malignant tumors. Smoking is one of the most important causes of NSCLC, which contributes not only to the initiation of NSCLC but also to its progression. The identification of specific biomarkers assoc...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2024-03-01
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| Series: | Journal of Cardiothoracic Surgery |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s13019-024-02625-x |
| _version_ | 1797247012522950656 |
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| author | Hong-Zhen Zheng Xiang Miao Jing Chang Hai Zhou Jing-Jian Zhang Hui-Min Mo Qin Jia |
| author_facet | Hong-Zhen Zheng Xiang Miao Jing Chang Hai Zhou Jing-Jian Zhang Hui-Min Mo Qin Jia |
| author_sort | Hong-Zhen Zheng |
| collection | DOAJ |
| description | Abstract Background Non-small cell lung cancer (NSCLC) is the leading cause of morality among all malignant tumors. Smoking is one of the most important causes of NSCLC, which contributes not only to the initiation of NSCLC but also to its progression. The identification of specific biomarkers associated with smoking will promote diagnosis and treatment. Methods Data mining was used to identify the smoking associated gene SERPINB12. CCK8 assays, colony formation assays, a mouse xenograft model and transwell assays were performed to measure the biological functions of SERPINB12 in NSCLC. GSEA, luciferase reporter assays and immunofluorescence were conducted to explore the potential molecular mechanisms of SERPINB12 in NSCLC. Results In this study, by data mining the TCGA database, we found that SERPINB12 was greatly upregulated in NSCLC patients with cigarette consumption behavior, while the expression level was positively correlated with disease grade and poor prognosis. SERPINB12 is a kind of serpin peptidase inhibitor, but its function in malignant tumors remains largely unknown. Functionally, knockdown of SERPINB12 observably inhibited the proliferation and metastasis of NSCLC cells in vitro and in vivo. Moreover, downregulation of SERPINB12 attenuated Wnt signaling by inhibiting the nuclear translocation of β-catenin, which explained the molecular mechanism underlying tumor progression. Conclusions In conclusion, SERPINB12 functions as a tumorigenesis factor, which could be a promising biomarker for NSCLC patients with smoking behavior, as well as a therapeutic target. |
| first_indexed | 2024-04-24T19:51:56Z |
| format | Article |
| id | doaj.art-a0d8f7349a6d4044a17e2090c0a212d9 |
| institution | Directory Open Access Journal |
| issn | 1749-8090 |
| language | English |
| last_indexed | 2024-04-24T19:51:56Z |
| publishDate | 2024-03-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Cardiothoracic Surgery |
| spelling | doaj.art-a0d8f7349a6d4044a17e2090c0a212d92024-03-24T12:33:35ZengBMCJournal of Cardiothoracic Surgery1749-80902024-03-0119111010.1186/s13019-024-02625-xSmoking behavior associated upregulation of SERPINB12 promotes proliferation and metastasis via activating WNT signaling in NSCLCHong-Zhen Zheng0Xiang Miao1Jing Chang2Hai Zhou3Jing-Jian Zhang4Hui-Min Mo5Qin Jia6Department of Respiratory Medicine, Shidong HospitalDepartment of Respiratory Medicine, Shidong HospitalDepartment of Respiratory Medicine, Shidong HospitalDepartment of Respiratory Medicine, Shidong HospitalDepartment of Respiratory Medicine, Shidong HospitalDepartment of Respiratory Medicine, Shidong HospitalDepartment of Respiratory Medicine, Shidong HospitalAbstract Background Non-small cell lung cancer (NSCLC) is the leading cause of morality among all malignant tumors. Smoking is one of the most important causes of NSCLC, which contributes not only to the initiation of NSCLC but also to its progression. The identification of specific biomarkers associated with smoking will promote diagnosis and treatment. Methods Data mining was used to identify the smoking associated gene SERPINB12. CCK8 assays, colony formation assays, a mouse xenograft model and transwell assays were performed to measure the biological functions of SERPINB12 in NSCLC. GSEA, luciferase reporter assays and immunofluorescence were conducted to explore the potential molecular mechanisms of SERPINB12 in NSCLC. Results In this study, by data mining the TCGA database, we found that SERPINB12 was greatly upregulated in NSCLC patients with cigarette consumption behavior, while the expression level was positively correlated with disease grade and poor prognosis. SERPINB12 is a kind of serpin peptidase inhibitor, but its function in malignant tumors remains largely unknown. Functionally, knockdown of SERPINB12 observably inhibited the proliferation and metastasis of NSCLC cells in vitro and in vivo. Moreover, downregulation of SERPINB12 attenuated Wnt signaling by inhibiting the nuclear translocation of β-catenin, which explained the molecular mechanism underlying tumor progression. Conclusions In conclusion, SERPINB12 functions as a tumorigenesis factor, which could be a promising biomarker for NSCLC patients with smoking behavior, as well as a therapeutic target.https://doi.org/10.1186/s13019-024-02625-xSERPINB12NSCLCWnt signalingProliferationMetastasis |
| spellingShingle | Hong-Zhen Zheng Xiang Miao Jing Chang Hai Zhou Jing-Jian Zhang Hui-Min Mo Qin Jia Smoking behavior associated upregulation of SERPINB12 promotes proliferation and metastasis via activating WNT signaling in NSCLC Journal of Cardiothoracic Surgery SERPINB12 NSCLC Wnt signaling Proliferation Metastasis |
| title | Smoking behavior associated upregulation of SERPINB12 promotes proliferation and metastasis via activating WNT signaling in NSCLC |
| title_full | Smoking behavior associated upregulation of SERPINB12 promotes proliferation and metastasis via activating WNT signaling in NSCLC |
| title_fullStr | Smoking behavior associated upregulation of SERPINB12 promotes proliferation and metastasis via activating WNT signaling in NSCLC |
| title_full_unstemmed | Smoking behavior associated upregulation of SERPINB12 promotes proliferation and metastasis via activating WNT signaling in NSCLC |
| title_short | Smoking behavior associated upregulation of SERPINB12 promotes proliferation and metastasis via activating WNT signaling in NSCLC |
| title_sort | smoking behavior associated upregulation of serpinb12 promotes proliferation and metastasis via activating wnt signaling in nsclc |
| topic | SERPINB12 NSCLC Wnt signaling Proliferation Metastasis |
| url | https://doi.org/10.1186/s13019-024-02625-x |
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