OncoTargets and Therapy (Feb 2019)
Bioinformatic analysis of miR-4792 regulates Radix Tetrastigma hemsleyani flavone to inhibit proliferation, invasion, and induce apoptosis of A549 cells
Abstract
Peigang Liu,1,2 Jinbao Pu,2 Junhui Zhang,3 Zhilu Chen,4 Kemin Wei,2,4,* Lian’gen Shi1,* 1College of Animal Sciences, Zhejiang University, Hangzhou, Zhejiang, People’s Republic of China; 2Department of Chinese Medicine, Zhejiang Academy of Traditional Chinese Medicine, Hangzhou, Zhejiang, People’s Republic of China; 3RuoHeng Family Farm, Zhejiang Dou Dou Bao Traditional Chinese Medicine Research Co., Ltd, Taizhou, Zhejiang, People’s Republic of China; 4Department of Hematology, Zhejiang Provincial Tongde Hospital, Hangzhou, Zhejiang, People’s Republic of China *These authors contributed equally to this work Background: Radix Tetrastigma hemsleyani, a kind of Chinese medicinal herb, contains multiple medicinal ingredients and can exert a variety of pharmacological activities. Our previous study revealed that miR-4792 was significantly upregulated in Radix Tetrastigma hemsleyani flavone (RTHF)-treated A549 cells; however, the regulatory mechanism of RTHF-treated A549 cells remains unclear.Materials and methods: In this study, we investigated the antitumor mechanism and regulatory pathway of miR-4792 in RTHF-treated A549 cells, and the target genes were predicted and pathway enrichment of miR-4792 was performed using bioinformatic analysis.Results: Our results confirmed that the upregulated expression of miR-4792 could inhibit cell proliferation and invasion, provoke cell cycle arrest, and induce apoptosis in A549 cells. Gene Ontology analysis showed that target genes of miR-4792 were enriched in protein binding, cytosol, cytoplasm, plasma membrane, and metal ion binding. Kyoto Encyclopedia of Genes and Genomes analysis showed that target genes of miR-4792 were enriched in aminoacyl-tRNA biosynthesis, AGE–RAGE signaling pathway in diabetic complications, sphingolipid signaling pathway, neuroactive ligand–receptor interaction, glycosaminoglycan degradation, and regulation of lipolysis in adipocytes. Additionally, FOXC1 was identified as an important target gene of miR-4792 in RTHF-treated A549 cells, and miR-4792 may be the target of some apoptotic-related proteins involved in induction of apoptosis in A549 cells by RTHF. Moreover, the intracellular Ca2+ levels of A549 cells were increased after RTHF treatment, which may be involved in the anticancer regulatory process of miR-4792 in RTHF-treated A549 cells. Conclusion: These findings suggest a novel therapeutic approach for lung cancer that will be investigated in future studies. Keywords: Radix Tetrastigma hemsleyani, flavone, miR-4792, GO, KEGG, FOXC1, potential therapeutic agents
