Dataset Information

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.

SUBMITTER: Wang R

PROVIDER: S-EPMC9385326 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature

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Publications

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

Wang Rui R Yi Junxuan J Gao Hui H Wei Xinfeng X Shao Lihong L Wang Mingwei M Xu Weiqiang W Yin Xiaoshu X Shen Yannan Y Wang Zhicheng Z Wei Wei W Jin Shunzi S

Oxidative medicine and cellular longevity 20220810

<h4>Background</h4>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.<h4>Methods</h4>Radiation-resistant cell models (A549-RR and H1299-RR) were made using fractionated high-dose irra ...[more]

PMID: 35993027

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Project description:Vertebrate locomotor circuitry contains distinct classes of ventral spinal cord neurons which each have particular functional properties. While we know some of the genes expressed by each of these cell types, we do not yet know how several of these neurons are specified. Here, we investigate the functions of Tal1, Gata2a, and Gata3 transcription factors in the development of two of these populations of neurons with important roles in locomotor circuitry: V2b neurons and cerebrospinal fluid-contacting Kolmer-Agduhr (KA) neurons (also called CSF-cNs). Our data provide the first demonstration, in any vertebrate, that Tal1 and Gata3 are required for correct development of KA and V2b neurons, respectively. We also uncover differences in the genetic regulation of V2b cell development in zebrafish compared to mouse. In addition, we demonstrate that Sox1a and Sox1b are expressed by KA and V2b neurons in zebrafish, which differs from mouse, where Sox1 is expressed by V2c neurons. KA neurons can be divided into ventral KA″ neurons and more dorsal KA' neurons. Consistent with previous morpholino experiments, our mutant data suggest that Tal1 and Gata3 are required in KA' but not KA″ cells, whereas Gata2a is required in KA″ but not KA' cells, even though both of these cell types co-express all three of these transcription factors. In gata2a mutants, cells in the KA″ region of the spinal cord lose expression of most KA″ genes and there is an increase in the number of cells expressing V3 genes, suggesting that Gata2a is required to specify KA″ and repress V3 fates in cells that normally develop into KA″ neurons. On the other hand, our data suggest that Gata3 and Tal1 are both required for KA' neurons to differentiate from progenitor cells. In the KA' region of these mutants, cells no longer express KA' markers and there is an increase in the number of mitotically-active cells. Finally, our data demonstrate that all three of these transcription factors are required for later stages of V2b neuron differentiation and that Gata2a and Tal1 have different functions in V2b development in zebrafish than in mouse.

Dataset Information

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

Background

Methods

Results

Conclusions

Publications

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

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