Paclitaxel-Induced Inhibition of NSCLC Invasion and Migration via RBFOX3-Mediated circIGF1R Biogenesis

Background: We previously reported that circIGF1R is significantly downregulated in non-small cell lung cancer (NSCLC) cells and tissues. It inhibits cancer cell invasion and migration, although the underlying molecular mechanisms remain elusive. Methods: : The invasion and migration of NSCLC cells was analyzed by routine in vivo and in vitro functional assays. Fluorescent in situ hybridization, luciferase reporter assay, RNA pull-down assay and RNA immunoprecipitation (RIP) assay were performed to explore the molecular mechanisms. Mechanism of action of paclitaxel-induced RBFOX3-mediated inhibition of NSCLC invasion and migration was investigated through in vitro and in vivo experiments. Results: : We found that circIGF1R regulated Van-Gogh-like 2 (VANGL2) expression as a Competing endogenous RNA (ceRNA) by “sponging” miR-1270, and inhibited the invasion and migration progression of NSCLC cells by inhibiting the Wnt pathway via the miR-1270/VANGL2 axis. Furthermore, RNA binding protein fox-1 homolog 3 (RBFOX3) promoted circIGF1R biogenesis through binding to the IGF1R pre-mRNA. RBFOX3 inhibits the migration and invasion ability of PC9 cells and A549 cells by increasing the biogenesis of circIGF1R. The chemotherapeutic drug paclitaxel inhibited NSCLC invasion and migration by inducing RBFOX3-mediated circIGF1R biogenesis. Conclusions: : RBFOX3 inhibits the invasion and migration of NSCLC cells through the circIGF1R/ miR-1270/VANGL2 axis, circIGF1R has the potential to serve as a biomarker and therapeutic target for NSCLC.