Loss of CDKN2A at chromosome 9 has a poor clinical prognosis and promotes lung cancer progression
Abstract Objective This study aimed to identify critical genes involved in the tumor biology of lung cancer via datamining of The Cancer Genome Atlas (TCGA) with special focus on gene copy number variation. Methods Genomic deletion and amplification were analyzed with cBioportal online tools. Relati...
| Príomhchruthaitheoirí: | , , , , , , |
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| Formáid: | Alt |
| Teanga: | English |
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Wiley
2020-12-01
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| Sraith: | Molecular Genetics & Genomic Medicine |
| Ábhair: | |
| Rochtain ar líne: | https://doi.org/10.1002/mgg3.1521 |
| _version_ | 1827345896216461312 |
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| author | Wei Liu Congwen Zhuang Tengfei Huang Shengsheng Yang Meiqing Zhang Baoquan Lin Yi Jiang |
| author_facet | Wei Liu Congwen Zhuang Tengfei Huang Shengsheng Yang Meiqing Zhang Baoquan Lin Yi Jiang |
| author_sort | Wei Liu |
| collection | DOAJ |
| description | Abstract Objective This study aimed to identify critical genes involved in the tumor biology of lung cancer via datamining of The Cancer Genome Atlas (TCGA) with special focus on gene copy number variation. Methods Genomic deletion and amplification were analyzed with cBioportal online tools. Relative expression of Cyclin Dependent Kinase Inhibitor 2A (CDKN2A) was analyzed by both real‐time polymerase chain reaction (PCR) and Western blot. The abundance of methylthioadenosine phosphorylase (MTAP) and epithelial‐mesenchymal transition markers were analyzed by real‐time PCR. Cell proliferation was determined by cell counting kit‐8 method and cell viability was measured with 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide assay. The cell migration and invasion were measured with transwell chamber assay, and migrative capacity was further evaluated by wound healing assay. Results We found the frequent loss of CDKN2A was associated with its downregulation in lung cancer, and siRNA‐mediated CDNKN2A knockdown significantly stimulated cell proliferation, invasion, and migration. Mechanistically, we unraveled that MTAP, which was positively correlated with CDKN2A, predominantly mediated the antitumoral function of CDKN2A in lung cancer. Conclusion Our study consolidated the involvement of CDKN2A‐MTAP signaling in the context of lung cancer. |
| first_indexed | 2024-03-07T23:19:24Z |
| format | Article |
| id | doaj.art-dfc7585cb283450b985a0b51df9dab2f |
| institution | Directory Open Access Journal |
| issn | 2324-9269 |
| language | English |
| last_indexed | 2024-03-07T23:19:24Z |
| publishDate | 2020-12-01 |
| publisher | Wiley |
| record_format | Article |
| series | Molecular Genetics & Genomic Medicine |
| spelling | doaj.art-dfc7585cb283450b985a0b51df9dab2f2024-02-21T08:38:03ZengWileyMolecular Genetics & Genomic Medicine2324-92692020-12-01812n/an/a10.1002/mgg3.1521Loss of CDKN2A at chromosome 9 has a poor clinical prognosis and promotes lung cancer progressionWei Liu0Congwen Zhuang1Tengfei Huang2Shengsheng Yang3Meiqing Zhang4Baoquan Lin5Yi Jiang6Department of Respiratory and Critical Care Medicine The 900th Hospital of Joint Logistic Support Force Fuzhou Fujian ChinaDepartment of Respiratory and Critical Care Medicine The 900th Hospital of Joint Logistic Support Force Fuzhou Fujian ChinaDepartment of Respiratory and Critical Care Medicine The 900th Hospital of Joint Logistic Support Force Fuzhou Fujian ChinaDepartment of Respiratory and Critical Care Medicine The 900th Hospital of Joint Logistic Support Force Fuzhou Fujian ChinaDepartment of Respiratory and Critical Care Medicine The 900th Hospital of Joint Logistic Support Force Fuzhou Fujian ChinaDepartment of Thoracic Surgery The 900th Hospital of Joint Logistic Support Force Fuzhou Fujian ChinaDepartment of Hepatobiliary Surgery The 900th Hospital of Joint Logistic Support Force Fuzhou Fujian ChinaAbstract Objective This study aimed to identify critical genes involved in the tumor biology of lung cancer via datamining of The Cancer Genome Atlas (TCGA) with special focus on gene copy number variation. Methods Genomic deletion and amplification were analyzed with cBioportal online tools. Relative expression of Cyclin Dependent Kinase Inhibitor 2A (CDKN2A) was analyzed by both real‐time polymerase chain reaction (PCR) and Western blot. The abundance of methylthioadenosine phosphorylase (MTAP) and epithelial‐mesenchymal transition markers were analyzed by real‐time PCR. Cell proliferation was determined by cell counting kit‐8 method and cell viability was measured with 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide assay. The cell migration and invasion were measured with transwell chamber assay, and migrative capacity was further evaluated by wound healing assay. Results We found the frequent loss of CDKN2A was associated with its downregulation in lung cancer, and siRNA‐mediated CDNKN2A knockdown significantly stimulated cell proliferation, invasion, and migration. Mechanistically, we unraveled that MTAP, which was positively correlated with CDKN2A, predominantly mediated the antitumoral function of CDKN2A in lung cancer. Conclusion Our study consolidated the involvement of CDKN2A‐MTAP signaling in the context of lung cancer.https://doi.org/10.1002/mgg3.1521CDKN2Acopy number variationlung cancerMTAP |
| spellingShingle | Wei Liu Congwen Zhuang Tengfei Huang Shengsheng Yang Meiqing Zhang Baoquan Lin Yi Jiang Loss of CDKN2A at chromosome 9 has a poor clinical prognosis and promotes lung cancer progression Molecular Genetics & Genomic Medicine CDKN2A copy number variation lung cancer MTAP |
| title | Loss of CDKN2A at chromosome 9 has a poor clinical prognosis and promotes lung cancer progression |
| title_full | Loss of CDKN2A at chromosome 9 has a poor clinical prognosis and promotes lung cancer progression |
| title_fullStr | Loss of CDKN2A at chromosome 9 has a poor clinical prognosis and promotes lung cancer progression |
| title_full_unstemmed | Loss of CDKN2A at chromosome 9 has a poor clinical prognosis and promotes lung cancer progression |
| title_short | Loss of CDKN2A at chromosome 9 has a poor clinical prognosis and promotes lung cancer progression |
| title_sort | loss of cdkn2a at chromosome 9 has a poor clinical prognosis and promotes lung cancer progression |
| topic | CDKN2A copy number variation lung cancer MTAP |
| url | https://doi.org/10.1002/mgg3.1521 |
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