CircZFR promotes pancreatic cancer progression through a novel circRNA-miRNA-mRNA pathway and stabilizing epithelial-mesenchymal transition protein

Pancreatic cancer (PC) ranks third in incidence and seventh in mortality among cancers worldwide. CircZFR has been implicated in various human cancers. Yet, how they affect PC progression is understudied. Herein, we demonstrated that circZFR was upregulated in PC tissues and cells, a feature that was correlated with the poor performance of patients with PC. Functional analyses elucidated that circZFR facilitated cell proliferation and enhanced tumorigenicity of PC. Moreover, we found that circZFR facilitated cell metastasis by differentially regulating the levels of proteins related to epithelial-mesenchymal transition (EMT). Mechanistic investigations revealed that circZFR sponged miR-375, thereby upregulating the downstream target gene, GREMLIN2 (GREM2). Additionally, circZFR knockdown resulted in attenuation of the JNK pathway, an effect that was reversed by GREM2 overexpression. Collectively, our findings implicate circZFR as a positive regulator of PC progression through the miR-375/GREM2/JNK axis.