Hsa_circ_0020378 targets miR-556-5p/MAPK1 to regulate osteosarcoma cell proliferation and migration

Gene. 2023 Mar 10:856:147135. doi: 10.1016/j.gene.2022.147135. Epub 2022 Dec 23.

Abstract

Osteosarcoma (OS) is still a disorder threatening children life. A growing number of evidences highlights the role of circular RNAs (circRNAs) during OS malignancy. Herein, we aimed to address the pathological contribution of the unrecognized circ_0020378 to OS progression. Analysis of the expression of circ_0020378, miR-556-5p, and MAPK1 in OS tissues and cells was performed using RT-qPCR or western blotting. CCK8, colony formation assays, and Tranwell migration assays were adopted to assess the OS cell viability, clone formation ability and migration. Tumor xenograft mouse model was used to assess the in vivo function of circ_0020378. The relationship between miR-556-5p and circ_0020378 or MAPK1 was discovered using luciferase reporter assays and RNA binding protein immunoprecipitation tests. In OS tissues and cells, circ_0020378 and MAPK1 were significantly elevated, although miR-556-5p expression exhibited a different pattern. Circ_0020378 silence attenuated OS cell proliferation, colony formation ability and migration in vitro, and retarded tumor growth in vivo. MiR-556-5p was targeted by circ_0020378. Furthermore, miR-556-5p inhibitor promoted the OS cell proliferation and migration, while this promoted malignant actions of OS cells were abrogated by circ_0020378 silence. Additionally, miR-556-5p directly bound to MAPK1, and MAPK1 silence exerted its inhibitory effect on OS cell proliferation and migration, and yet the inhibition was offset by miR-556-5p inhibitor. Circ_0020378 acts as a novel tumor promoter that controls OS growth by miR-556-5p/MAPK1 axis, suggesting circ_0020378/miR-556-5p/MAPK1 might be a novel target for OS intervention.

Keywords: Circ_0020378; MAPK1; Osteosarcoma; miR-556-5p.

MeSH terms

  • Animals
  • Blotting, Western
  • Bone Neoplasms*
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Proliferation / genetics
  • Disease Models, Animal
  • Humans
  • Mice
  • MicroRNAs* / genetics
  • Mitogen-Activated Protein Kinase 1
  • Osteosarcoma* / genetics

Substances

  • MicroRNAs
  • MAPK1 protein, human
  • Mitogen-Activated Protein Kinase 1
  • MIRN556 microRNA, human