Hsa_circ_0128846 knockdown attenuates the progression of pancreatic cancer by targeting miR-1270/NR3C1 axis

The considerable role of circular RNAs (circRNAs) make them prospective biomarkers in cancer therapy. Our study aimed to unveil the function of circ_0128846 in pancreatic cancer (PC). The expressions of circ_0128846, miR-1270 and NR3C1 mRNA were measured via RT-qPCR. The expressions of NR3C1 protein and apoptosis-related markers (Bax and Bcl-2) were measured via western blotting. CCK-8, colony-forming, or wound healing assay was respectively utilized to identify cell proliferation, growth and migration. Xenograft model was developed to evaluate tumor growth affected by circ_0128846 in vivo. The putative binding between miR-1270 and circ_0128846 or NR3C1 was testified by dual-luciferase reporter, RIP or pull-down assay. Circ_0128846 showed elevated expression in PC. Circ_0128846 deficiency restrained cancer cell proliferation, colony formation and migratory ability, enhanced cell apoptotic rate, and also impeded tumor development in vivo. Circ_0128846 directly targeted miR-1270 whose expression was declined in PC. The suppressive effects of silencing circ_0128846 on PC cell malignant phenotypes were largely reversed by miR-1270 inhibition. NR3C1 was targeted by miR-1270 and was highly regulated in PC. The repressive effects of NR3C1 knockdown on PC cell malignant phenotypes were partly abolished by miR-1270 inhibition. Circ_0128846 deficiency blocked PC progression via mediating the miR-1270/NR3C1 pathway, which partly illustrated PC pathogenesis.

Automated summary

The study aimed to investigate the role of circ_0128846 in pancreatic cancer (PC) and its interaction with miR-1270 and NR3C1. The results showed that circ_0128846 was highly expressed in PC and its deficiency inhibited cancer cell proliferation, colony formation, migration, and tumor growth. Circ_0128846 directly targeted miR-1270, which was downregulated in PC. Inhibition of miR-1270 partially reversed the suppressive effects of circ_0128846 silencing on PC progression. Furthermore, miR-1270 targeted NR3C1, and its knockdown partially abolished the repressive effects on PC cell malignant phenotypes. Our findings suggest that circ_0128846 functions as a potential biomarker and mediator in PC through the miR-1270/NR3C1 pathway.