Circular RNA circ_0020123 promotes non-small cell lung cancer progression by acting as a ceRNA for miR-488-3p to regulate ADAM9 expression

Biochem Biophys Res Commun. 2019 Jul 23;515(2):303-309. doi: 10.1016/j.bbrc.2019.05.158. Epub 2019 May 29.

Abstract

Circular RNAs (circRNAs) is a class of non-coding RNA with important functions in tumor development and progression. In the previous study, circ_0020123 was found to be an elevated circRNA in non-small cell lung cancer (NSCLC) tissues screened by high-throughput sequencing. In the current work, we uncovered the clinical significance, biological functions and mechanism of circ_0020123 in NSCLC. The expression profile of circ_0020123 was measured by RT-qPCR. Correlations between circ_0020123 expression and patients' clinical features were evaluated. Cell viability, apoptosis, migration and invasion were detected by cell counting kit-8 (CCK-8), flow cytometric and transwell assay, respectively. Bioinformatics database and luciferase reporter gene assays were utilized to identify the mechanisms of circ_0020123. The results revealed elevation of circ_0020123 in tissue specimens and cells than the nontumorous tissues and 16HBE, separately. The enhancement of circ_0020123 in tumor tissues correlated with positive lymph node metastasis, advanced TNM stages, and adverse prognosis for NSCLC patients. Functionally, silencing of circ_0020123 distinctly suppressed the growth, migration and invasion and inhibited the apoptosis of A549 cells. On the contrary, when circ_0020123 expression was ectopically expressed, the above effects were significantly strengthened in H1299 cell line. For the mechanism exploration, circ_0020123 could sponge miR-488-3p to release its inhibition on ADAM9 expression. Moreover, the functional role of circ_0020123 is partly dependent on its regulation of ADAM9 proved by rescue assays. Taken together, our findings provide the possibility that circ_0020123 may be a new target for NSCLC prognosis prediction and therapy.

Keywords: ADAM9; Circular RNA; NSCLC; circ_0020123; miR-488–3p.

MeSH terms

  • A549 Cells
  • ADAM Proteins / genetics*
  • ADAM Proteins / metabolism
  • Apoptosis / genetics
  • Carcinogenesis / genetics
  • Carcinoma, Non-Small-Cell Lung / genetics*
  • Carcinoma, Non-Small-Cell Lung / metabolism
  • Carcinoma, Non-Small-Cell Lung / pathology
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Proliferation / genetics
  • Disease Progression
  • Humans
  • Lung Neoplasms / genetics*
  • Lung Neoplasms / metabolism
  • Lung Neoplasms / pathology
  • Membrane Proteins / genetics*
  • Membrane Proteins / metabolism
  • MicroRNAs / genetics*
  • MicroRNAs / metabolism
  • Neoplasm Invasiveness / genetics
  • Neoplasm Invasiveness / pathology
  • RNA, Circular / genetics*
  • RNA, Circular / metabolism

Substances

  • MIRN488 microRNA, human
  • Membrane Proteins
  • MicroRNAs
  • Mirn182 microRNA, human
  • RNA, Circular
  • ADAM Proteins
  • ADAM9 protein, human