Circ_0006006 facilitates non-small cell lung cancer progression by modulating miR-924/SRSF7 axis

J Gene Med. 2022 May;24(5):e3411. doi: 10.1002/jgm.3411. Epub 2022 Mar 21.

Abstract

Background: Non-small cell lung cancer (NSCLC) is an aggressive tumor with high mortality. Circular RNAs played crucial roles in the development of cancers, including NSCLC. In the present study, the action of circ_0006006 in NSCLC was investigated.

Methods: Using a real-time quantitative polymerase chain reaction, the relative gene expression was detected. The structure of circ_0006006 was identified using RNase R digestion and actinomycin D treatment. The functional role of circ_0006006 in cell proliferation, migration, invasion, apoptosis and angiogenesis was explored using cell counting kit-8, 5-ethynyl-2'-deoxyuridine, colony formation, wound healing, transwell, flow cytometry and tube formation assays, respectively. Using western blotting, the relative proteins expression was measured. Dual-luciferase reporter and RNA immunoprecipitation assays were employed to verify the correlation between microRNA-924 (miR-924) and circ_0006006 or serine/arginine-rich splicing factor 7 (SRSF7). Xenograft tumor experiment was used to investigate the effect of circ_0006006 on tumor growth in vivo. An immunohistochemistry assay was performed to detect Ki-67, Bax, Bcl-2 and SRSF7 expression in tissues of mice.

Results: Circ_0006006 was increased in NSCLC tissues and cells. Loss-of-function assays demonstrated that circ_0006006 silencing repressed proliferative ability, cell migration and invasion, and angiogenesis, as well as promoted cell apoptosis, in A549 and H1299 cells. Follow-up mechanism experiments depicted that circ_0006006 sponged miR-924 and miR-924 inhibitor rescued the circ_0006006 knockdown-mediated inhibition effect on the progression of NSCLC. Additionally, the inhibition effect of circ_0006006 knockdown on SRSF7 expression was reversed by miR-924 inhibitor. Moreover, the suppressive effect of miR-924 on NSCLC progression was reversed by SRSF7 overexpression. Xenograft tumor experiment unveiled that circ_0006006 knockdown inhibited tumor growth in vivo.

Conclusions: Circ_0006006 stimulated NSCLC progression by targeting miR-924 to regulate SRSF7 expression.

Keywords: SRSF7; circ_0006006; miR-924; non-small cell lung cancer.

MeSH terms

  • Animals
  • Carcinoma, Non-Small-Cell Lung* / metabolism
  • Cell Movement / genetics
  • Cell Proliferation / genetics
  • Humans
  • Lung Neoplasms* / pathology
  • Mice
  • MicroRNAs* / genetics
  • MicroRNAs* / metabolism
  • RNA, Circular / genetics
  • Serine-Arginine Splicing Factors

Substances

  • MicroRNAs
  • RNA, Circular
  • SRSF7 protein, human
  • Serine-Arginine Splicing Factors