MicroRNA‑487b‑3p inhibits osteosarcoma chemoresistance and metastasis by targeting ALDH1A3

Oncol Rep. 2020 Dec;44(6):2691-2700. doi: 10.3892/or.2020.7814. Epub 2020 Oct 19.

Abstract

Metastasis and chemoresistance indicate poor prognosis in patients with osteosarcoma (OS). In the present study, the expression level of microRNA(miR)‑487b‑3p in OS specimens and cell lines was found to be decreased, and the expression level of miR‑487b‑3p was associated with overall survival in patients with OS. The inhibition of miR‑487b‑3p stimulated OS cell migration and contributed to the development of chemoresistance. In contrast, the overexpression of miR‑487b‑3p significantly inhibited OS cell migration and enhanced the sensitivity of OS cells to doxorubicin treatment. In addition, the results from the present study revealed that the suppression of miR‑487b‑3p stimulates OS stemness, while the overexpression of miR‑487b‑3p suppresses OS stemness. Notably, in vivo experiments also revealed that the overexpression of miR‑487b‑3p inhibited cancer stem cell (CSC)‑induced tumor formation, and the combination treatment of miR‑487b‑3p and doxorubicin significantly inhibited CSC‑induced tumor growth. Furthermore, miR‑487b‑3p exerts its anticancer role by targeting aldehyde dehydrogenase 1 family member A3 in OS. Taken together, the results from the present study suggests that miR‑487b‑3p is a tumor suppressor and that the overexpression of miR‑487b‑3p is a novel strategy to inhibit tumor metastasis and chemoresistance in OS.

Keywords: microRNA-487b-3p; ALDH1A3; chemoresistance; metastasis; osteosarcoma.

Publication types

  • Observational Study

MeSH terms

  • Adult
  • Aged
  • Aldehyde Oxidoreductases / genetics*
  • Animals
  • Apoptosis / drug effects
  • Apoptosis / genetics
  • Biopsy
  • Bone Neoplasms / drug therapy*
  • Bone Neoplasms / genetics
  • Bone Neoplasms / mortality
  • Bone Neoplasms / pathology
  • Case-Control Studies
  • Cell Line, Tumor
  • Cell Movement / drug effects
  • Cell Movement / genetics
  • Cell Proliferation / drug effects
  • Cell Proliferation / genetics
  • Doxorubicin / pharmacology
  • Doxorubicin / therapeutic use
  • Drug Resistance, Neoplasm / genetics*
  • Female
  • Gene Expression Regulation, Neoplastic
  • Healthy Volunteers
  • Humans
  • Male
  • Mice
  • MicroRNAs / metabolism*
  • Middle Aged
  • Osteosarcoma / drug therapy*
  • Osteosarcoma / genetics
  • Osteosarcoma / mortality
  • Osteosarcoma / secondary
  • Survival Rate
  • Xenograft Model Antitumor Assays
  • Young Adult

Substances

  • MIRN487 microRNA, human
  • MicroRNAs
  • Doxorubicin
  • Aldehyde Oxidoreductases
  • aldehyde dehydrogenase (NAD(P)+)