Integrated Analysis of mRNA-seq and miRNA-seq to Identify c-MYC, YAP1 and miR-3960 as Major Players in the Anticancer Effects of Caffeic Acid Phenethyl Ester in Human Small Cell Lung Cancer Cell Line

Background: Caffeic Acid Phenethyl Ester (CAPE), an active extract of propolis, has recently been reported to have broad applications in various cancers. However, the effects of CAPE on Small Cell Lung Cancer (SCLC) are largely unknown. Therefore, the aim of this study was to determine the anti-proliferative effect of CAPE and explore the underlying molecular mechanisms in SCLC cells using high-throughput sequencing and bioinformatics analysis. Methods: Small-cell lung cancer H446 cells were treated with CAPE, and cell proliferation and apoptosis were then assessed. Additionally, the regulation mediated by miR-3960 after CAPE treatment was explored and the altered signaling pathways were predicted in a bioinformatics analysis. Results: CAPE significantly inhibited cell proliferation and induced apoptosis. CAPE decreased the expression of Yes-Associated Protein 1 (YAP1) and cellular myelocytomatosis oncogene (c-MYC) protein. Moreover, the upregulation of miR-3960 by CAPE contributed to CAPE-induced apoptosis. The knockdown of miR-3960 decreased the CAPE-induced apoptosis. Conclusion: We demonstrated the anti-cancer effect of CAPE in human SCLC cells and studied the mechanism by acquiring a comprehensive transcriptome profile of CAPE-treated cells.