Astragaloside IV exhibits anti-tumor function in gastric cancer via targeting circRNA dihydrolipoamide S-succinyltransferase (circDLST)/miR-489-3p/ eukaryotic translation initiation factor 4A1(EIF4A1) pathway.

Abstract

Astragaloside IV (AS-IV) is an inartificial saponin separated from astragalus membranaceus, which has exhibited key anti-tumor regulation in some cancers. Circular RNAs (circRNAs) are important regulators in malignant development of gastric cancer (GC). Herein, we focused on the molecular mechanism of AS-IV with circRNA dihydrolipoamide S-succinyltransferase (circDLST) in GC. CircDLST, microRNA-489-3p (miR-489-3p), and eukaryotic translation initiation factor 4A1 (EIF4A1) levels were detected by quantitative real-time polymerase-chain reaction and western blot. Cell functions were assessed by cell counting kit-8 assay, ethynyl-2'-deoxyuridine assay, colony formation assay, and transwell assay. The interaction between miR-489-3p and circDLST or EIF4A1 was analyzed by dual-luciferase reporter assay. Xenograft tumor assay was adopted to check the role of circDLST and AS-IV in vivo. CircDLST and EIF4A1 were upregulated but miR-489-3p was downregulated in GC cells. AS-IV restrained cell proliferation and metastasis in GC cells by downregulating circDLST. CircDLST served as a miR-489-3p sponge, and miR-489-3p inhibition reversed anti-tumor function of AS-IV. EIF4A1 was a target for miR-489-3p and circDLST sponged miR-489-3p to regulate EIF4A1. AS-IV suppressed GC cell progression via circDLST-mediated downregulation of EIF4A1. Also, AS-IV recued tumor growth in vivo via targeting circDLST to regulate miR-489-3p/EIF4A1 axis. AS-IV inhibited the development of GC through circDLST/miR-489-3p/EIF4A1 axis.

• Authors: Fagen Li, Ke Cao, Maoyun Wang, Yi Liu, Yin Zhang
• Journal: Bioengineered (Bioengineered) Vol. 13 Issue 4 Pg. 10111-10122 (04 2022) ISSN: 2165-5987 [Electronic] United States
• PMID: 35435117 (Publication Type: Journal Article)

Chemical References

• MIRN489 microRNA, human
• MicroRNAs
• Peptide Initiation Factors
• RNA, Circular
• Saponins
• Triterpenes
• dihydrolipoamide
• astragaloside A
• Thioctic Acid

Topics

• Humans
• MicroRNAs (genetics, metabolism)
• Peptide Initiation Factors
• RNA, Circular (genetics)
• Saponins (pharmacology)
• Stomach Neoplasms (drug therapy, genetics, pathology)
• Thioctic Acid (analogs & derivatives)
• Triterpenes