Ionizing Radiation Promotes Epithelial-Mesenchymal Transition Phenotype and Stem Cell Marker in The Lung adenocarcinoma: In Vitro and Bioinformatic Studiesc
Objective: Ionizing radiation (IR) is one of the major therapeutic approaches in the non-small cell lung cancer (NSCLC);however, it can paradoxically result in cancer progression likely through promoting epithelial-mesenchymal transition(EMT) and the cancer stem cell phenotype. Therefore, we aimed t...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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Royan Institute (ACECR), Tehran
2022-09-01
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| Series: | Cell Journal |
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| Online Access: | https://www.celljournal.org/article_253357_8284f91a242c25d18203c5debf44e745.pdf |
| _version_ | 1811209088066912256 |
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| author | Mehdi Raei Mahdi Bagheri Safieh Aghaabdollahian Masoud Ghorbani Afshin Sadeghi |
| author_facet | Mehdi Raei Mahdi Bagheri Safieh Aghaabdollahian Masoud Ghorbani Afshin Sadeghi |
| author_sort | Mehdi Raei |
| collection | DOAJ |
| description | Objective: Ionizing radiation (IR) is one of the major therapeutic approaches in the non-small cell lung cancer (NSCLC);however, it can paradoxically result in cancer progression likely through promoting epithelial-mesenchymal transition(EMT) and the cancer stem cell phenotype. Therefore, we aimed to determine whether IR promote EMT/CSC and toinvestigate the clinical relevance of EMT/CSC hallmark genes.Materials and Methods: In this experimental and bioinformatic study, A549 cell line was irradiated with a high dosage(6 Gy) or a fractionated regimen (2 Gy/day for 15 fractions). The EMT-related features, including cellular morphology,migratory and invasive capacities were evaluated using scratch assay and transwell migration/invasion assays. ThemRNA levels of EMT-related genes (CDH1, CDH2, SNAI1 and TWIST1), stemness-related markers (CD44, PROM1,and ALDH1A1) and the CDH2/CDH1 ratio were evaluated via real-time polymerase chain reaction (PCR). The clinicalsignificance of these genes was assessed in the lung adenocarcinoma (LUAD) samples using online databases.Results: Irradiation resulted in a dramatic elongation of cell shape and enhanced invasion and migration capabilities. These EMT-like alterations were accompanied with enhanced levels of SNAI1, CDH2, TWIST1, CD44, PROM1, and ALDH1A1 as well as an enhanced CDH2/CDH1 ratio. TCGA analysis revealed that, TWIST1, CDH1, PROM1 and CDH2 were upregulated; whereas, CD44, SNAI1 and ALDH1A1 were downregulated. Additionally, correlations between SNAI1-TWIST1, CDH2- TWIST1, CDH2-SNAI1, and ALDH1A1-PROM1 was positive. Kaplan-Meier survival analysis identified lower expression of CDH1, PROM1 and ALDH1A1 and increased expression of CDH2, SNAI1, and TWIST1 as well as CDH2/CDH1 ratio predict overall survival. Additionally, downregulation of ALDH1A1 and upregulation of CDH2, SNAI1 and TWIST1 could predict a shorter first progression.Conclusion: Altogether, these findings demonstrated that IR promotes EMT phenotype and stem cell markers in A549cell line and these genes could function as diagnostic or prognostic indicators in LUAD samples. |
| first_indexed | 2024-04-12T04:32:27Z |
| format | Article |
| id | doaj.art-7b90f8133f4547c690bcb9d3c2c3d2d3 |
| institution | Directory Open Access Journal |
| issn | 2228-5806 2228-5814 |
| language | English |
| last_indexed | 2024-04-12T04:32:27Z |
| publishDate | 2022-09-01 |
| publisher | Royan Institute (ACECR), Tehran |
| record_format | Article |
| series | Cell Journal |
| spelling | doaj.art-7b90f8133f4547c690bcb9d3c2c3d2d32022-12-22T03:47:53ZengRoyan Institute (ACECR), TehranCell Journal2228-58062228-58142022-09-0124952253010.22074/cellj.2022.8403253357Ionizing Radiation Promotes Epithelial-Mesenchymal Transition Phenotype and Stem Cell Marker in The Lung adenocarcinoma: In Vitro and Bioinformatic StudiescMehdi Raei0Mahdi Bagheri1Safieh Aghaabdollahian2Masoud Ghorbani3Afshin Sadeghi4Health Research Center, Life Style Institute, Baqiyatallah University of Medical Sciences, Tehran, IranStudent Research Committee, Baqiyatallah University of Medical Sciences, Tehran, IranDepartment of Nanobiotechnology, New Technologies Research Group, Pasteur Institute of Iran, Tehran, IranApplied Biotechnology Research Center, Baqiyatallah University of Medical Sciences, Tehran, IranStudent Research Committee, Baqiyatallah University of Medical Sciences, Tehran, IranObjective: Ionizing radiation (IR) is one of the major therapeutic approaches in the non-small cell lung cancer (NSCLC);however, it can paradoxically result in cancer progression likely through promoting epithelial-mesenchymal transition(EMT) and the cancer stem cell phenotype. Therefore, we aimed to determine whether IR promote EMT/CSC and toinvestigate the clinical relevance of EMT/CSC hallmark genes.Materials and Methods: In this experimental and bioinformatic study, A549 cell line was irradiated with a high dosage(6 Gy) or a fractionated regimen (2 Gy/day for 15 fractions). The EMT-related features, including cellular morphology,migratory and invasive capacities were evaluated using scratch assay and transwell migration/invasion assays. ThemRNA levels of EMT-related genes (CDH1, CDH2, SNAI1 and TWIST1), stemness-related markers (CD44, PROM1,and ALDH1A1) and the CDH2/CDH1 ratio were evaluated via real-time polymerase chain reaction (PCR). The clinicalsignificance of these genes was assessed in the lung adenocarcinoma (LUAD) samples using online databases.Results: Irradiation resulted in a dramatic elongation of cell shape and enhanced invasion and migration capabilities. These EMT-like alterations were accompanied with enhanced levels of SNAI1, CDH2, TWIST1, CD44, PROM1, and ALDH1A1 as well as an enhanced CDH2/CDH1 ratio. TCGA analysis revealed that, TWIST1, CDH1, PROM1 and CDH2 were upregulated; whereas, CD44, SNAI1 and ALDH1A1 were downregulated. Additionally, correlations between SNAI1-TWIST1, CDH2- TWIST1, CDH2-SNAI1, and ALDH1A1-PROM1 was positive. Kaplan-Meier survival analysis identified lower expression of CDH1, PROM1 and ALDH1A1 and increased expression of CDH2, SNAI1, and TWIST1 as well as CDH2/CDH1 ratio predict overall survival. Additionally, downregulation of ALDH1A1 and upregulation of CDH2, SNAI1 and TWIST1 could predict a shorter first progression.Conclusion: Altogether, these findings demonstrated that IR promotes EMT phenotype and stem cell markers in A549cell line and these genes could function as diagnostic or prognostic indicators in LUAD samples.https://www.celljournal.org/article_253357_8284f91a242c25d18203c5debf44e745.pdfdose fractionation lung neoplasmsepithelial-mesenchymal transitionneoplastic stem cellsradiotherapy |
| spellingShingle | Mehdi Raei Mahdi Bagheri Safieh Aghaabdollahian Masoud Ghorbani Afshin Sadeghi Ionizing Radiation Promotes Epithelial-Mesenchymal Transition Phenotype and Stem Cell Marker in The Lung adenocarcinoma: In Vitro and Bioinformatic Studiesc Cell Journal dose fractionation lung neoplasms epithelial-mesenchymal transition neoplastic stem cells radiotherapy |
| title | Ionizing Radiation Promotes Epithelial-Mesenchymal Transition Phenotype and Stem Cell Marker in The Lung adenocarcinoma: In Vitro and Bioinformatic Studiesc |
| title_full | Ionizing Radiation Promotes Epithelial-Mesenchymal Transition Phenotype and Stem Cell Marker in The Lung adenocarcinoma: In Vitro and Bioinformatic Studiesc |
| title_fullStr | Ionizing Radiation Promotes Epithelial-Mesenchymal Transition Phenotype and Stem Cell Marker in The Lung adenocarcinoma: In Vitro and Bioinformatic Studiesc |
| title_full_unstemmed | Ionizing Radiation Promotes Epithelial-Mesenchymal Transition Phenotype and Stem Cell Marker in The Lung adenocarcinoma: In Vitro and Bioinformatic Studiesc |
| title_short | Ionizing Radiation Promotes Epithelial-Mesenchymal Transition Phenotype and Stem Cell Marker in The Lung adenocarcinoma: In Vitro and Bioinformatic Studiesc |
| title_sort | ionizing radiation promotes epithelial mesenchymal transition phenotype and stem cell marker in the lung adenocarcinoma in vitro and bioinformatic studiesc |
| topic | dose fractionation lung neoplasms epithelial-mesenchymal transition neoplastic stem cells radiotherapy |
| url | https://www.celljournal.org/article_253357_8284f91a242c25d18203c5debf44e745.pdf |
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