CircDUS2L (circ_0039908) promotes lung adenocarcinoma progression by upregulating PGAM1 by acting as a miR-590-5p molecular sponge

J Biochem Mol Toxicol. 2023 Sep;37(9):e23406. doi: 10.1002/jbt.23406. Epub 2023 Jul 1.

Abstract

Lung adenocarcinoma (LUAD) is usually found at the metastatic stage. Circular RNA dihydrouridine synthase 2-like (DUS2L) (circDUS2L) has been discovered to be upregulated in LUAD. Nevertheless, the function of circDUS2L in LUAD has not been verified. Levels of circDUS2L, microRNA-590-5p (miR-590-5p), and phosphoglycerate mutase 1 (PGAM1) mRNA were analyzed using quantitative real-time polymerase chain reaction (RT-qPCR). Cell proliferation, apoptosis, metastasis, and invasion were assessed by 3-(4,5-Dimethylthiazol-2-yl)-2,5-Diphenyltetrazolium Bromide (MTT), colony formation, 5-ethynyl-2'-deoxyuridine (Edu), flow cytometry, and transwell assays. Protein levels were detected by western blotting. Cell glycolysis was analyzed by measuring cell glucose consumption, lactate production, and extracellular acidification rate (ECAR). The regulatory mechanism of circDUS2L in LUAD cells was analyzed by bioinformatics analysis, dual-luciferase reporter, RNA pull-down, and RNA immunoprecipitation (RIP) assays. Xenograft assay was conducted to confirm the function of circDUS2L in vivo. CircDUS2L was highly expressed in LUAD tissues and cells. CircDUS2L silencing constrained xenograft tumor growth in vivo. CircDUS2L knockdown induced apoptosis, repressed viability, colony formation, proliferation, metastasis, invasion, and glycolysis of LUAD cells in vitro by releasing miR-590-5p via functioning as a miR-590-5p sponge. MiR-590-5p was lowly expressed in LUAD tissues and cells, and miR-590-5p mimic curbed malignant behaviors and glycolysis of LUAD cells by targeting PGAM1. PGAM1 was overexpressed in LUAD tissues and cells, and circDUS2L sponged miR-590-5p to regulate PGAM1 expression. CircDUS2L elevated PGAM1 expression through functioning as a miR-590-5p sponge, thus driving malignant behaviors and glycolysis of LUAD cells.

Keywords: LUAD; PGAM1; circDUS2L; miR-590-5p.

MeSH terms

  • Adenocarcinoma of Lung* / genetics
  • Adenocarcinoma*
  • Cell Line, Tumor
  • Cell Proliferation
  • Humans
  • Lung Neoplasms* / genetics
  • MicroRNAs* / genetics
  • Phosphoglycerate Mutase / genetics
  • RNA, Circular / genetics

Substances

  • Phosphoglycerate Mutase
  • RNA, Circular
  • MicroRNAs
  • MIRN590 microRNA, human