沉默 TAB182 通过下调 A549 NSCLC 细胞中的 EGFR 抑制细胞 EMT、迁移和侵袭,Molecular Biology Reports

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沉默 TAB182 通过下调 A549 NSCLC 细胞中的 EGFR 抑制细胞 EMT、迁移和侵袭
Molecular Biology Reports ( IF 2.6 ) Pub Date : 2023-01-23 , DOI: 10.1007/s11033-022-08176-5
Shaozheng Wang ₁ , Hejiang Guo ₁ , Jin Jia _{1,

2} , Wen Zhang _{1,

2} , Shanshan Gao ₁ , Hua Guan ₁ , Huan He _{1,

3} , Pingkun Zhou _{1,

2}

Affiliation

背景

TAB182 在癌组织中过表达，与肺癌患者的总体生存率低相关。从机制上讲，TAB182 参与 DNA 损伤修复并赋予肿瘤细胞放射和化学抗性。然而，其在非小细胞肺癌 (NSCLC) 中的作用仍不清楚。

方法和结果

使用 A549 NSCLC 细胞生成具有稳定 TAB182 敲低 (KD) 的细胞，我们证明耗尽 TAB182 会抑制细胞 EMT、增殖、集落形成、迁移和侵袭。TCGA 数据库的分析显示 TAB182 和 EGFR 之间呈正相关，EGFR 是一种公认的 NSCLC 癌蛋白。然后，我们证实沉默 TAB182 会降低 mRNA 和蛋白质水平的 EGFR 表达。此外，据报道，TAB182 和 EGFR 均可恢复电离辐射 (IR) 引发的 DNA 损伤。我们验证了 IR 提高了 EGFR 的蛋白质水平，并且沉默 TAB182 可以减轻 IR 诱导的 EGFR 上调。此外，过表达 EGFR 可消除 TAB182 KD 对 A549 细胞的 EMT、迁移和侵袭的抑制作用。

结论

我们的数据表明 EGFR 表达受 TAB182 调节，TAB182 的下调具有通过降低 EGFR 来抑制 EMT、迁移和侵袭的新功能，表明 TAB182 可以调节 NSCLC 的恶性进展。

"点击查看英文标题和摘要"

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

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.

更新日期：2023-01-23

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