AUTHOR=Chen Lin , Li Qirong , Jiang Ziping , Li Chengshun , Hu Haobo , Wang Tiedong , Gao Yan , Wang Dongxu 

TITLE=Chrysin Induced Cell Apoptosis Through H19/let-7a/COPB2 Axis in Gastric Cancer Cells and Inhibited Tumor Growth

JOURNAL=Frontiers in Oncology

VOLUME=11

YEAR=2021

URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2021.651644

DOI=10.3389/fonc.2021.651644

ISSN=2234-943X

ABSTRACT=<sec><title>Background</title><p>Chrysin is a natural flavone that is present in honey and has exhibited anti-tumor properties. It has been widely studied as a therapeutic agent for the treatment of various types of cancers. The objectives of this present study were to elucidate how chrysin regulates non-coding RNA expression to exert anti-tumor effects in gastric cancer cells.</p></sec><sec><title>Methods</title><p>Through the use of RNA sequencing, we investigated the differential expression of mRNAs in gastric cancer cells treated with chrysin. Furthermore, <italic>COPB2, H19</italic> and let-7a overexpression and knockdown were conducted. Other features, including cell growth, apoptosis, migration and invasion, were also analyzed. Knockout of the <italic>COPB2</italic> gene was generated using the CRISPR/Cas9 system for tumor growth analysis <italic>in vivo</italic>.</p></sec><sec><title>Results</title><p>Our results identified <italic>COPB2</italic> as a differentially expressed mRNA that is down-regulated following treatment with chrysin. Moreover, the results showed that chrysin can induce cellular apoptosis and inhibit cell migration and invasion. To further determine the underlying mechanism of COPB2 expression, we investigated the expression of the long non-coding RNA (lncRNA) <italic>H19</italic> and microRNA let-7a. Our results showed that treatment with chrysin significantly increased let-7a expression and reduced the expression of <italic>H19</italic> and <italic>COPB2</italic>. In addition, our results demonstrated that reduced expression of <italic>COPB2</italic> markedly promotes cell apoptosis. Finally, <italic>in vivo</italic> data suggested that <italic>COPB2</italic> expression is related to tumor growth.</p></sec><sec><title>Conclusions</title><p>This study suggests that chrysin exhibited anti-tumor effects through a <italic>H19</italic>/let-7a/<italic>COPB2</italic> axis.</p></sec>