MiR-141-3p overexpression suppresses the malignancy of osteosarcoma by targeting FUS to degrade LDHB

Biosci Rep. 2020 Jun 26;40(6):BSR20193404. doi: 10.1042/BSR20193404.

Abstract

Osteosarcoma (OS) is a common malignant bone cancer. Lactate dehydrogenase B (LDHB) has been revealed to act as a tumor promoter in several cancers. It is also revealed to be correlated with poor prognosis in OS, but its molecular mechanism in OS remains veiled. Our work illustrated that LDHB was overexpressed in OS tissues and cells, and it could enhance cell proliferation, migration, and invasion in OS. Subsequently, it was confirmed that fused in sarcoma (FUS) could bind with LDHB to positively regulate the stability of LDHB messenger RNA (mRNA). Besides, FUS expression was revealed to be elevated in OS tissues and positively correlate with LDHB expression. Furthermore, miR-141-3p, down-regulated in OS cells, was identified as the upstream regulator of FUS in OS cells. Besides, miR-141-3p overexpression decreased mRNA and protein levels of FUS and LDHB. More importantly, overexpression of miR-141-3p could impair FUS overexpression-mediated promotion on LDHB mRNA stability and expression. Finally, rescue assays indicated that miR-141-3p regulated OS cells cellular process via regulating LDHB. In sum, miR-141-3p targets FUS to degrade LDHB, thereby attenuating the malignancy of OS cells.

Keywords: FUS; LDHB; miR-141-3p; osteosarcoma.

MeSH terms

  • Bone Neoplasms / enzymology*
  • Bone Neoplasms / genetics
  • Bone Neoplasms / pathology
  • Cell Line, Tumor
  • Cell Movement
  • Cell Proliferation
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Isoenzymes / genetics
  • Isoenzymes / metabolism
  • L-Lactate Dehydrogenase / genetics
  • L-Lactate Dehydrogenase / metabolism*
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Neoplasm Invasiveness
  • Osteosarcoma / enzymology*
  • Osteosarcoma / genetics
  • Osteosarcoma / pathology
  • RNA Stability
  • RNA-Binding Protein FUS / genetics
  • RNA-Binding Protein FUS / metabolism*
  • Signal Transduction
  • Up-Regulation

Substances

  • FUS protein, human
  • Isoenzymes
  • MIRN141 microRNA, human
  • MicroRNAs
  • RNA-Binding Protein FUS
  • L-Lactate Dehydrogenase
  • lactate dehydrogenase 1