Integrative RNA-Seq and ATAC-Seq Analysis Reveals the Migration-Associated Genes Involved in Antitumor Effects of Herbal Medicine Feiyanning on Lung Cancer Cells.

Chenyang Wang,Yonglin Peng,Pengxiao Li,Xiaoting Wu,Xiaodong Zhao,Sheng Tan,Ming Zhang,Ruiqi Liu

doi:10.3389/fgene.2021.799099

Abstract

Lung cancer is one of the leading causes of cancer-associated death in the world. It is of great importance to explore new therapeutic targets. Traditional Chinese medicine formula Feiyanning has been clinically administered in China for more than a decade and raised attention due to its anticancer effect in lung cancer. However, the underlying molecular mechanisms remain to be elucidated. In the present study, we carried out cellular and molecular assays to examine the antitumor activities and understand the mechanism of the Feiyanning formula in lung cancer cells. The cellular viability of Feiyanning-treated lung cancer cells was evaluated by Cell Counting Kit-8. The effect of the Feiyanning formula on cellular migration and invasion of lung cancer cells was examined by wound healing and transwell assays. Transcriptome and chromatin accessibility analysis by RNA-seq and ATAC-seq was performed to investigate the underlying molecular mechanisms. Our results revealed that the Feiyanning formula inhibited the cellular activities of proliferation, migration, and invasion in non-small cell lung cancer cell lines A549, H1975, and 95D. Furthermore, we observed that the transcriptional activity of the migration-associated genes was downregulated upon Feiyanning formula treatment in non-small cell lung cancer cells. The chromatin accessibility of the Feiyanning-treated lung cancer genome tended to decrease, and the regulation of the cellular component movement biological process and PI3K-AKT pathway were enriched among these altered genomic regions. Taken together, the present study suggested that Feiyanning formula exerted the antitumor effects by modulating the expression and chromatin accessibility levels of migration-associated genes.

Highlights

Lung cancer is a malignancy with high morbidity and mortality around the world (Siegel et al, 2018; Cao et al, 2020)
CCK-8 assay was performed to examine the effect of the FYN formula on the viability of lung cancer cell lines A549, H1975, and 95D
We observed that the FYN formula exerted antitumor effects by inhibiting the cellular proliferation, migration, and invasion of A549, H1975, and 95D cells

Summary

Introduction

Lung cancer is a malignancy with high morbidity and mortality around the world (Siegel et al, 2018; Cao et al, 2020). Lung cancer patients are routinely treated with surgery (Hoy et al, 2019), radiation therapy (Aokage et al, 2017; Gensheimer and Loo, 2017; Fitzgerald and Simone, 2020), chemotherapy (Nagasaka and Gadgeel., 2018), immunotherapy (Steven et al, 2016; Doroshow et al, 2019), targeted therapy (Hirsch et al, 2017; Duma et al, 2019), or a combination of these treatments. These treatments have both advantages and disadvantages.

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Conclusion