CircSMARCA5 silencing impairs cell proliferation and invasion via the miR-17-3p-EGFR signaling in lung adenocarcinoma

Life Sci. 2023 May 1:320:121560. doi: 10.1016/j.lfs.2023.121560. Epub 2023 Mar 7.

Abstract

Aims: Circular RNAs are widely expressed in various cancers and play important roles in tumorigenesis and tumor progression. The function and mechanism of circSMARCA5 in lung adenocarcinoma however remains unclear.

Main methods: QRT-PCR analysis was applied for determining circSMARCA5 expression in lung adenocarcinoma patient tumor tissues and cells. Molecular biological assays were used for investigating the role of circSMARCA5 in lung adenocarcinoma progression. Luciferase reporter and bioinformatics assays were used for identifying the underlying mechanism.

Key findings: In this study, we observed that circSMARCA5 expression was decreased in lung adenocarcinoma tissues but silencing of circSMARCA5 in lung adenocarcinoma cells inhibited cell proliferation, colony formation, migration and invasion. Mechanistically, we found EGFR, c-MYC and p21 were down-regulated upon circSMARCA5 knockdown. MiR-17-3p efficiently down- regulated EGFR expression via directly binding to EGFR mRNA.

Significance: These studies suggest that circSMARCA5 functions as an oncogene via targeting miR-17-3p-EGFR axis and may represent a promising therapeutic target for lung adenocarcinoma.

Keywords: EGFR; Invasion; Lung cancer; Proliferation; circSMARCA5.

MeSH terms

  • Adenocarcinoma of Lung* / genetics
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Proliferation / genetics
  • ErbB Receptors / genetics
  • ErbB Receptors / metabolism
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Lung Neoplasms* / pathology
  • MicroRNAs* / metabolism

Substances

  • MicroRNAs
  • ErbB Receptors
  • EGFR protein, human
  • MIRN17 microRNA, human