circNINL facilitates aerobic glycolysis, proliferation, invasion, and migration in lung cancer by sponging miR-3918 to mediate FGFR1 expression

Abstract

Previously characterized as an oncogenic player in breast cancer, the function of circular RNA NINL (circNINL) in lung cancer (LC) remained elusive. This study aimed to delineate the biological role of circNINL in LC and to unveil its potential molecular mechanisms. We discovered elevated expression levels of circNINL and Fibroblast Growth Factor Receptor 1 (FGFR1) concomitant with diminished expression of microRNA-3918 (miR-3918) in LC specimens. Knockdown of circNINL led to a marked decrease in cell proliferation, migration, invasion, and aerobic glycolysis, alongside an upsurge in apoptosis in LC cells. Either downregulation of miR-3918 or overexpression of FGFR1 mitigated the suppressive impact of circNINL knockdown on LC pathogenesis. Mechanistic studies validated that circNINL served as a competitive endogenous RNA for miR-3918, thus influencing FGFR1 expression. Further, in vivo experiments using nude mouse xenograft models underscored that silencing circNINL substantially curtailed tumor growth in LC. Collectively, these findings illuminate that circNINL exacerbates LC malignancy via the miR-3918/FGFR1 axis, a process integrally linked with the activation of aerobic glycolysis.

Graphical Abstract

Highlights

1. CircNINL and FGFR1 are highly expressed and miR-3918 is poorly expressed in lung cancer.

2. Knockdown of circNINL inhibits lung cancer growth and aerobic glycolysis.

3. Knockdown of miR-3918 or overexpression of FGFR1 reverses the inhibitory effect of knockdown of circNINL on lung cancer.

4. circNINL acts as a sponge for miR-3918 to mediate FGFR1 expression.