{"title":"Tankyrase 2 能促进肺癌细胞恶变。","authors":"Ying Wang, Yong-Jun Zhang","doi":"10.5306/wjco.v15.i6.755","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Tankyrase 2 (TNKS2) is a potential candidate molecular target for the prognosis and treatment of non-small cell lung cancer (NSCLC), but its biological functions are unclear.</p><p><strong>Aim: </strong>To investigate the biological functions of TNKS2 in NSCLC.</p><p><strong>Methods: </strong>Using a lentiviral vector, we generated H647 model cells with TNKS2 knockdown by RNA interference and A549 model cells with TNKS2 overexpression by transfection with a TNKS2 overexpressing plasmid. Increased and decreased expression levels of TNKS2 in the two cell lines were verified using real-time reverse transcriptase-polymerase chain reaction and Western blot analyses. Cell apoptosis, proliferation, and migration were determined using flow cytometry, carboxyfluorescein succinimidyl ester staining, and scratch assay, respectively. Immunofluorescence staining was conducted to examine TNKS2 and β-catenin expression levels in the two transfected cell lines and the non-transfected cells.</p><p><strong>Results: </strong>TNKS2 mRNA and protein expression was significantly higher in the highly malignant NCI-H647 cells, while it remained at a low level in the less malignant A549 cells. Lentivirus-mediated overexpression of TNKS2 in A549 cells resulted in a 3-fold increase in gene expression and a 1.7-fold increase in protein expression (<i>P</i> < 0.01). Conversely, shRNA interference targeting <i>TNKS2</i> Led to an 8-fold decrease in gene expression and a 3-fold decrease in protein expression (<i>P</i> < 0.01) in NCI-H647 cells. Furthermore, the cell apoptosis rate was significantly reduced (50%) and cell migration rate was increased (35%) in the TNKS2 overexpression group than in the control group (<i>P</i> < 0.05). In contrast, sh<i>TNKS2</i> promoted apoptosis by more than one fold and reduced migration by 60% (<i>P</i> < 0.05). Immunofluorescence analysis revealed enhanced nuclear localization of β-catenin fluorescence signal associated with high TNKS2 expression levels. Western blot analysis investigating TNKS2/β-catenin-related proteins indicated consistent changes between TNKS2 and β-catenin expression in lung cancer cells, whereas Axin displayed an opposite trend (<i>P</i> < 0.05).</p><p><strong>Conclusion: </strong>The obtained results revealed that TNKS2 may serve as an adverse prognostic factor and a potential therapeutic target in NSCLC.</p>","PeriodicalId":23802,"journal":{"name":"World journal of clinical oncology","volume":"15 6","pages":"755-764"},"PeriodicalIF":2.6000,"publicationDate":"2024-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11212605/pdf/","citationCount":"0","resultStr":"{\"title\":\"Tankyrase 2 promotes lung cancer cell malignancy.\",\"authors\":\"Ying Wang, Yong-Jun Zhang\",\"doi\":\"10.5306/wjco.v15.i6.755\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>Tankyrase 2 (TNKS2) is a potential candidate molecular target for the prognosis and treatment of non-small cell lung cancer (NSCLC), but its biological functions are unclear.</p><p><strong>Aim: </strong>To investigate the biological functions of TNKS2 in NSCLC.</p><p><strong>Methods: </strong>Using a lentiviral vector, we generated H647 model cells with TNKS2 knockdown by RNA interference and A549 model cells with TNKS2 overexpression by transfection with a TNKS2 overexpressing plasmid. Increased and decreased expression levels of TNKS2 in the two cell lines were verified using real-time reverse transcriptase-polymerase chain reaction and Western blot analyses. Cell apoptosis, proliferation, and migration were determined using flow cytometry, carboxyfluorescein succinimidyl ester staining, and scratch assay, respectively. Immunofluorescence staining was conducted to examine TNKS2 and β-catenin expression levels in the two transfected cell lines and the non-transfected cells.</p><p><strong>Results: </strong>TNKS2 mRNA and protein expression was significantly higher in the highly malignant NCI-H647 cells, while it remained at a low level in the less malignant A549 cells. Lentivirus-mediated overexpression of TNKS2 in A549 cells resulted in a 3-fold increase in gene expression and a 1.7-fold increase in protein expression (<i>P</i> < 0.01). Conversely, shRNA interference targeting <i>TNKS2</i> Led to an 8-fold decrease in gene expression and a 3-fold decrease in protein expression (<i>P</i> < 0.01) in NCI-H647 cells. Furthermore, the cell apoptosis rate was significantly reduced (50%) and cell migration rate was increased (35%) in the TNKS2 overexpression group than in the control group (<i>P</i> < 0.05). In contrast, sh<i>TNKS2</i> promoted apoptosis by more than one fold and reduced migration by 60% (<i>P</i> < 0.05). Immunofluorescence analysis revealed enhanced nuclear localization of β-catenin fluorescence signal associated with high TNKS2 expression levels. Western blot analysis investigating TNKS2/β-catenin-related proteins indicated consistent changes between TNKS2 and β-catenin expression in lung cancer cells, whereas Axin displayed an opposite trend (<i>P</i> < 0.05).</p><p><strong>Conclusion: </strong>The obtained results revealed that TNKS2 may serve as an adverse prognostic factor and a potential therapeutic target in NSCLC.</p>\",\"PeriodicalId\":23802,\"journal\":{\"name\":\"World journal of clinical oncology\",\"volume\":\"15 6\",\"pages\":\"755-764\"},\"PeriodicalIF\":2.6000,\"publicationDate\":\"2024-06-24\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11212605/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"World journal of clinical oncology\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.5306/wjco.v15.i6.755\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q3\",\"JCRName\":\"ONCOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"World journal of clinical oncology","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.5306/wjco.v15.i6.755","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"ONCOLOGY","Score":null,"Total":0}
Background: Tankyrase 2 (TNKS2) is a potential candidate molecular target for the prognosis and treatment of non-small cell lung cancer (NSCLC), but its biological functions are unclear.
Aim: To investigate the biological functions of TNKS2 in NSCLC.
Methods: Using a lentiviral vector, we generated H647 model cells with TNKS2 knockdown by RNA interference and A549 model cells with TNKS2 overexpression by transfection with a TNKS2 overexpressing plasmid. Increased and decreased expression levels of TNKS2 in the two cell lines were verified using real-time reverse transcriptase-polymerase chain reaction and Western blot analyses. Cell apoptosis, proliferation, and migration were determined using flow cytometry, carboxyfluorescein succinimidyl ester staining, and scratch assay, respectively. Immunofluorescence staining was conducted to examine TNKS2 and β-catenin expression levels in the two transfected cell lines and the non-transfected cells.
Results: TNKS2 mRNA and protein expression was significantly higher in the highly malignant NCI-H647 cells, while it remained at a low level in the less malignant A549 cells. Lentivirus-mediated overexpression of TNKS2 in A549 cells resulted in a 3-fold increase in gene expression and a 1.7-fold increase in protein expression (P < 0.01). Conversely, shRNA interference targeting TNKS2 Led to an 8-fold decrease in gene expression and a 3-fold decrease in protein expression (P < 0.01) in NCI-H647 cells. Furthermore, the cell apoptosis rate was significantly reduced (50%) and cell migration rate was increased (35%) in the TNKS2 overexpression group than in the control group (P < 0.05). In contrast, shTNKS2 promoted apoptosis by more than one fold and reduced migration by 60% (P < 0.05). Immunofluorescence analysis revealed enhanced nuclear localization of β-catenin fluorescence signal associated with high TNKS2 expression levels. Western blot analysis investigating TNKS2/β-catenin-related proteins indicated consistent changes between TNKS2 and β-catenin expression in lung cancer cells, whereas Axin displayed an opposite trend (P < 0.05).
Conclusion: The obtained results revealed that TNKS2 may serve as an adverse prognostic factor and a potential therapeutic target in NSCLC.
期刊介绍：
The WJCO is a high-quality, peer reviewed, open-access journal. The primary task of WJCO is to rapidly publish high-quality original articles, reviews, editorials, and case reports in the field of oncology. In order to promote productive academic communication, the peer review process for the WJCO is transparent; to this end, all published manuscripts are accompanied by the anonymized reviewers’ comments as well as the authors’ responses. The primary aims of the WJCO are to improve diagnostic, therapeutic and preventive modalities and the skills of clinicians and to guide clinical practice in oncology. Scope: Art of Oncology, Biology of Neoplasia, Breast Cancer, Cancer Prevention and Control, Cancer-Related Complications, Diagnosis in Oncology, Gastrointestinal Cancer, Genetic Testing For Cancer, Gynecologic Cancer, Head and Neck Cancer, Hematologic Malignancy, Lung Cancer, Melanoma, Molecular Oncology, Neurooncology, Palliative and Supportive Care, Pediatric Oncology, Surgical Oncology, Translational Oncology, and Urologic Oncology.
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