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

Bioengineered. 2022 Apr;13(4):10111-10122. doi: 10.1080/21655979.2022.2063664.

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.

Keywords: Astragaloside IV; EIF4A1; circDLST; gastric cancer; miR-489-3p.

MeSH terms

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

Substances

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

Grants and funding

The author(s) reported that there is no funding associated with the work featured in this article.