B7-H6 enhances F-actin rearrangement by targeting c-MYC activation to promote medulloblastoma migration and invasion

Med Oncol. 2023 Jan 24;40(3):85. doi: 10.1007/s12032-023-01947-5.

Abstract

Medulloblastoma (MB) is children's most common primary malignant primitive neuro-ectodermal tumor. Group 3 MB showed a higher propensity to metastasis, which is molecularly characterized by c-MYC gene amplification. The activation of c-MYC promotes the remodeling of the F-actin cytoskeleton to enhance metastasis. The B7 homologue 6 (B7-H6) is associated with the manifold essential hallmarks of tumorigenesis. In this study, we will explore whether B7-H6 regulates the reorganization of F-actin by elevating the c-MYC expression to promote metastasis. The Daoy cell line was used to act as the cell model of medulloblastoma. Small interfering RNA and the plasmid were used to downregulate and upregulate the expression of B7-H6 in Daoy cells. Transwell assays with/without the matrigel matrix were used to detect migration and invasion of Daoy cells. Western blots were used to detect the expression of related proteins. Immunofluorescence staining was used to observe the impact of B7-H6 on the c-MYC /F-actin axis. B7-H6 improved migration and invasion in the Daoy cell line. B7-H6 enhanced the rearrangement of F-actin and activated the expression of MMP-9 and MMP-2. B7-H6 promoted the remodeling of F-actin by targeting c-MYC activation to reinforce migration and invasion. B7-H6 acts as a promoter of migration and invasion in medulloblastoma by activating the c-MYC /F-actin axis.

Keywords: B7-H6; F-actin; Medulloblastoma; Migration and invasion; c-MYC.

MeSH terms

  • Actin Cytoskeleton / metabolism
  • Actin Cytoskeleton / pathology
  • Actins / genetics
  • Actins / metabolism
  • B7-1 Antigen / metabolism
  • Cell Adhesion Molecules / metabolism
  • Cell Line, Tumor
  • Cerebellar Neoplasms* / genetics
  • Cerebellar Neoplasms* / metabolism
  • Child
  • Humans
  • Medulloblastoma* / genetics
  • Medulloblastoma* / metabolism
  • Medulloblastoma* / pathology

Substances

  • Actins
  • Cell Adhesion Molecules
  • B7-1 Antigen