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Silencing TAB182 inhibits cell EMT, migration and invasion by downregulating EGFR in A549 NSCLC cells

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Abstract

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.

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Funding

This study was supported by the National Natural Science Foundation of China, 31870847 and 32171238 to Pingkun Zhou, Postdoctoral Research Foundation of China, 2021M693965 to Huan He

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Authors and Affiliations

  1. Department of Radiation Toxicology and Oncology, Beijing Key Laboratory for Radiobiology, Beijing Institute of Radiation Medicine, Beijing, 100850, China

    Shaozheng Wang, Hejiang Guo, Jin Jia, Wen Zhang, Shanshan Gao, Hua Guan, Huan He & Pingkun Zhou

  2. School of Medicine, University of South China, Hengyang, 421001, China

    Jin Jia, Wen Zhang & Pingkun Zhou

  3. NHC Key Laboratory of Radiobiology, School of Public Health, Jilin University, Changchun, 130021, China

    Huan He

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  1. Shaozheng Wang
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Correspondence to Huan He or Pingkun Zhou.

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Wang, S., Guo, H., Jia, J. et al. Silencing TAB182 inhibits cell EMT, migration and invasion by downregulating EGFR in A549 NSCLC cells. Mol Biol Rep 50, 3073–3083 (2023). https://doi.org/10.1007/s11033-022-08176-5

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