GATA3 Exerts Distinct Transcriptional Functions to Regulate Radiation Resistance in A549 and H1299 Cells.

Abstract

Background:

Radiation resistance of lung cancer cells is a vital factor affecting the curative effect of lung cancer. Transcription factor GATA3 is involved in cell proliferation, invasion, and migration and is significantly expressed in a variety of malignancies. However, the molecular mechanism governing GATA3 regulation in lung cancer cells' radiation resistance is unknown.

Methods:

Radiation-resistant cell models (A549-RR and H1299-RR) were made using fractionated high-dose irradiation. Use clone formation, CCK-8, F-actin staining, cell cycle detection, and other experiments to verify whether the model is successfully constructed. Cells were transiently transfected with knockdown or overexpression plasmid. To explore the relationship between GATA3/H3K4me3 and target genes, we used ChIP-qPCR, ChIP-seq, and dual luciferase reporter gene experiments. Xenograft tumor models were used to evaluate the effect of GATA3 depletion on the tumorigenic behavior of lung cancer cells.

Results:

We report that transcription factors GATA3 and H3K4me3 coactivate NRP1 gene transcription when A549 cells develop radiation resistance. However, the mechanism of radiation resistance in H1299 cells is that GATA3 acts as a transcription inhibitor. The decrease of GATA3 will promote the increase of NRP1 transcription, in which H3K4me3 does not play a leading role.

Conclusions:

GATA3, an upstream transcriptional regulator of NRP1 gene, regulates the radioresistance of A549 and H1299 cells by opposite mechanisms, which provides a new target for radiotherapy of lung cancer.

• Authors: Rui Wang, Junxuan Yi, Hui Gao, Xinfeng Wei, Lihong Shao, Mingwei Wang, Weiqiang Xu, Xiaoshu Yin, Yannan Shen, Zhicheng Wang, Wei Wei, Shunzi Jin
• Journal: Oxidative medicine and cellular longevity (Oxid Med Cell Longev) Vol. 2022 Pg. 9174111 ( 2022) ISSN: 1942-0994 [Electronic] United States
• PMID: 35993027 (Publication Type: Journal Article)
• Copyright: Copyright © 2022 Rui Wang et al.

Chemical References

• GATA3 Transcription Factor
• GATA3 protein, human

Topics

• A549 Cells
• Cell Line, Tumor
• Cell Proliferation (genetics)
• GATA3 Transcription Factor (genetics, metabolism, therapeutic use)
• Gene Expression Regulation, Neoplastic
• Humans
• Lung Neoplasms (drug therapy, genetics, radiotherapy)
• Radiation Tolerance (genetics)