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

Sci Rep. 2023 Feb 16;13(1):2792. doi: 10.1038/s41598-023-28439-w.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Biological Assay
  • Blotting, Western
  • Cell Line, Tumor
  • Cell Proliferation / genetics
  • Humans
  • MicroRNAs* / genetics
  • Pancreatic Neoplasms* / genetics
  • RNA, Circular* / genetics
  • Receptors, Glucocorticoid

Substances

  • MicroRNAs
  • MIRN1270 microRNA, human
  • NR3C1 protein, human
  • Receptors, Glucocorticoid
  • RNA, Circular