TY - JOUR ID - 253357 TI - Ionizing Radiation Promotes Epithelial-Mesenchymal Transition Phenotype and Stem Cell Marker in The Lung adenocarcinoma: In Vitro and Bioinformatic Studiesc JO - Cell Journal (Yakhteh) JA - CELLJ LA - en SN - 2228-5806 AU - Raei, Mehdi AU - Bagheri, Mahdi AU - Aghaabdollahian, Safieh AU - Ghorbani, Masoud AU - Sadeghi, Afshin AD - Health Research Center, Life Style Institute, Baqiyatallah University of Medical Sciences, Tehran, Iran AD - Student Research Committee, Baqiyatallah University of Medical Sciences, Tehran, Iran AD - Department of Nanobiotechnology, New Technologies Research Group, Pasteur Institute of Iran, Tehran, Iran AD - Applied Biotechnology Research Center, Baqiyatallah University of Medical Sciences, Tehran, Iran Y1 - 2022 PY - 2022 VL - 24 IS - 9 SP - 522 EP - 530 KW - Dose Fractionation Lung Neoplasms KW - epithelial-mesenchymal transition KW - Neoplastic Stem Cells KW - Radiotherapy DO - 10.22074/cellj.2022.8403 N2 - 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. UR - https://www.celljournal.org/article_253357.html L1 - https://www.celljournal.org/article_253357_8284f91a242c25d18203c5debf44e745.pdf ER -