Overexpressed circ-RPL15 predicts poor survival and promotes the progression of gastric cancer via regulating miR-502-3p/OLFM4/STAT3 pathway

Biomed Pharmacother. 2020 Jul:127:110219. doi: 10.1016/j.biopha.2020.110219. Epub 2020 May 20.

Abstract

Background: Increasing studies have revealed that circular RNAs (circRNAs) contribute to gastric cancer (GC) progression. The circular RNA ribosomal protein L15 (circ-RPL15) is involved in chronic lymphocytic leukemia. However, its expression and functions in GC remain elusive.

Methods: The expression of circ-RPL15 in human GC tissues and adjacent normal tissues, human gastric cancer cell lines (MGC-803, BGC-823, MGN-28, SGC-7901, AGS) and normal gastric mucosal epithelial cell line (GES-1) were detected by RT-PCR. The relationship between circ-RPL15 level and clinical-pathological indicators were also analyzed. Gain- of function experiments of circ-RPL15 and miR-502-3p were conducted to verify their roles in mediating GC cell proliferation, apoptosis and metastasis. Also, the downstream mechanisms of circ-RPL15 were predicted by bioinformatics analysis, and the interactions between circ-RPL15 and miR-502-3p, miR-502-3p and OLFM4 were verified by dual luciferase reporter gene assay and RNA FISH.

Results: circ-RPL15 was upregulated in GC tissues and cell lines, and the overexpressed circ-RPL15 was correlated with poorer survival of GC patients. Functionally, circ-RPL15 upregulation distinctly promoted the proliferation, migration and invasion of GC cells and inhibited apoptosis. Mechanistically, circ-RPL15 functioned as a competitive endogenous RNA via sponging miR-502-3p and activated OLFM4/STAT3 pathway.

Conclusion: circ-RPL15 promotes GC progression and predicts poor prognosis of GC patients, and regulates the malignant phenotypes of GC cells by mediating the miR-502-3p/OLFM4/STAT3 axis.

Keywords: Gastric cancer; OLFM3; STAT3; circ_RPL15; miR-502-3p.

MeSH terms

  • Apoptosis / physiology
  • Cell Line, Tumor
  • Cell Movement / physiology
  • Cell Proliferation / physiology
  • Disease Progression
  • Female
  • Gene Expression Regulation, Neoplastic / physiology*
  • Granulocyte Colony-Stimulating Factor / metabolism*
  • Humans
  • Male
  • MicroRNAs / metabolism*
  • Middle Aged
  • Ribosomal Proteins / biosynthesis
  • Ribosomal Proteins / physiology*
  • STAT3 Transcription Factor / metabolism*
  • Stomach Neoplasms / metabolism
  • Stomach Neoplasms / pathology
  • Stomach Neoplasms / physiopathology*
  • Survival Analysis
  • Up-Regulation

Substances

  • MIRN502 microRNA, human
  • MicroRNAs
  • OLFM4 protein, human
  • RPL15 protein, human
  • Ribosomal Proteins
  • STAT3 Transcription Factor
  • STAT3 protein, human
  • Granulocyte Colony-Stimulating Factor