PMID- 36689051 OWN - NLM STAT- MEDLINE DCOM- 20230330 LR - 20230330 IS - 1573-4978 (Electronic) IS - 0301-4851 (Linking) VI - 50 IP - 4 DP - 2023 Apr TI - Silencing TAB182 inhibits cell EMT, migration and invasion by downregulating EGFR in A549 NSCLC cells. PG - 3073-3083 LID - 10.1007/s11033-022-08176-5 [doi] AB - BACKGROUND: TAB182 is overexpressed in cancerous tissues and correlated with poor overall survival in lung cancer patients. Mechanistically, TAB182 participates in DNA damage repair and endows tumour cells with radio- and chemoresistance. However, its role in non-small cell lung cancer (NSCLC) remains unclear. METHODS AND RESULTS: Cells with stable TAB182 knockdown (KD) were generated using A549 NSCLC cells, and we demonstrated that depleting TAB182 inhibits cell EMT, proliferation, colony formation, migration and invasion. Analysis of the TCGA database showed a positive correlation between TAB182 and EGFR, a well-established NSCLC oncoprotein. Then, we verified that silencing TAB182 decreases EGFR expression at both the mRNA and protein levels. Moreover, both TAB182 and EGFR were reported to restore ionizing radiation (IR)-triggered DNA damage. We validated that IR elevates the protein level of EGFR and that silencing TAB182 can alleviate IR-induced EGFR upregulation. Furthermore, overexpressing EGFR abrogates the inhibitory effects of TAB182 KD on EMT, migration, and invasion in A549 cells. CONCLUSIONS: Our data demonstrated that EGFR expression is regulated by TAB182 and downregulation of TAB182 has a novel function to repress EMT, migration and invasion by decreasing EGFR, indicating TAB182 could regulate the malignant progression of NSCLC. CI - (c) 2023. The Author(s), under exclusive licence to Springer Nature B.V. FAU - Wang, Shaozheng AU - Wang S AD - Department of Radiation Toxicology and Oncology, Beijing Key Laboratory for Radiobiology, Beijing Institute of Radiation Medicine, Beijing, 100850, China. FAU - Guo, Hejiang AU - Guo H AD - Department of Radiation Toxicology and Oncology, Beijing Key Laboratory for Radiobiology, Beijing Institute of Radiation Medicine, Beijing, 100850, China. FAU - Jia, Jin AU - Jia J AD - Department of Radiation Toxicology and Oncology, Beijing Key Laboratory for Radiobiology, Beijing Institute of Radiation Medicine, Beijing, 100850, China. AD - School of Medicine, University of South China, Hengyang, 421001, China. FAU - Zhang, Wen AU - Zhang W AD - Department of Radiation Toxicology and Oncology, Beijing Key Laboratory for Radiobiology, Beijing Institute of Radiation Medicine, Beijing, 100850, China. AD - School of Medicine, University of South China, Hengyang, 421001, China. FAU - Gao, Shanshan AU - Gao S AD - Department of Radiation Toxicology and Oncology, Beijing Key Laboratory for Radiobiology, Beijing Institute of Radiation Medicine, Beijing, 100850, China. FAU - Guan, Hua AU - Guan H AD - Department of Radiation Toxicology and Oncology, Beijing Key Laboratory for Radiobiology, Beijing Institute of Radiation Medicine, Beijing, 100850, China. FAU - He, Huan AU - He H AUID- ORCID: 0000-0001-8123-5765 AD - Department of Radiation Toxicology and Oncology, Beijing Key Laboratory for Radiobiology, Beijing Institute of Radiation Medicine, Beijing, 100850, China. hehuan@jlu.edu.cn. AD - NHC Key Laboratory of Radiobiology, School of Public Health, Jilin University, Changchun, 130021, China. hehuan@jlu.edu.cn. FAU - Zhou, Pingkun AU - Zhou P AD - Department of Radiation Toxicology and Oncology, Beijing Key Laboratory for Radiobiology, Beijing Institute of Radiation Medicine, Beijing, 100850, China. zhoupk@bmi.ac.cn. AD - School of Medicine, University of South China, Hengyang, 421001, China. zhoupk@bmi.ac.cn. LA - eng GR - 31870847/National Natural Science Foundation of China/ GR - 32171238/National Natural Science Foundation of China/ GR - 2021M693965/Postdoctoral Research Foundation of China/ PT - Journal Article DEP - 20230123 PL - Netherlands TA - Mol Biol Rep JT - Molecular biology reports JID - 0403234 RN - EC 2.7.10.1 (EGFR protein, human) RN - EC 2.7.10.1 (ErbB Receptors) RN - 0 (TNKS1BP1 protein, human) SB - IM MH - Humans MH - A549 Cells MH - *Carcinoma, Non-Small-Cell Lung/pathology MH - Cell Line, Tumor MH - Cell Movement/genetics MH - Cell Proliferation/genetics MH - Epithelial-Mesenchymal Transition/genetics MH - ErbB Receptors/genetics/metabolism MH - Gene Expression Regulation, Neoplastic/genetics MH - *Lung Neoplasms/metabolism OTO - NOTNLM OT - Cell invasion OT - Cell migration OT - EGFR OT - EMT OT - Lung cancer cells OT - TAB182 EDAT- 2023/01/24 06:00 MHDA- 2023/03/29 06:05 CRDT- 2023/01/23 11:17 PHST- 2022/09/07 00:00 [received] PHST- 2022/12/06 00:00 [accepted] PHST- 2023/03/29 06:05 [medline] PHST- 2023/01/24 06:00 [pubmed] PHST- 2023/01/23 11:17 [entrez] AID - 10.1007/s11033-022-08176-5 [pii] AID - 10.1007/s11033-022-08176-5 [doi] PST - ppublish SO - Mol Biol Rep. 2023 Apr;50(4):3073-3083. doi: 10.1007/s11033-022-08176-5. Epub 2023 Jan 23.