miR-487b and TRAK2 that form an axis to regulate the aggressiveness of osteosarcoma, are potential therapeutic targets and prognostic biomarkers

J Biochem Mol Toxicol. 2020 Aug;34(8):e22511. doi: 10.1002/jbt.22511. Epub 2020 Apr 8.

Abstract

To investigate the effect of microRNA-487b (miR-487b) as well as the underlying mechanism in osteosarcoma (OS). Data downloaded from the Gene Expression Omnibus (GEO) database were used to analyze the expression and prognostic value of miR-487b/TRAK2. Cell counting kit-8, colony formation, and transwell assays were performed to investigate the biological functions of miR-487b and TRAK2. Luciferase reporter assay was applied to confirm the interactions between miR-487b and TRAK2. miR-487b was overexpressed in OS tissues and was inversely associated with the prognosis of OS patients. We discovered that miR-487b could contribute to the proliferative, clonogenic, invasive, and migratory capabilities of OS cells. Through target prediction using miRWalk and differential expression analysis based on the GEO data set, trafficking kinesin protein 2 (TRAK2) was recognized as a potential target of miR-487b, which was further verified by luciferase reporter assay. The expression of TRAK2 was decreased in OS tissues compared with normal tissues and was positively correlated with the prognosis of OS patients. A negative relevance was presented between the expression of miR-487b and TRAK2 in OS cells. Of note, further mechanistic analyses indicated that TRAK2 was implicated in the regulatory effect of miR-487b on the cell malignant behaviors in OS. To sum up, these results demonstrated that miR-487b played an oncogenic role in OS progression via directly targeting TRAK2, which could advance the development of cancer treatment.

Keywords: TRAK2; miR-487b; osteosarcoma; prognosis; progression.

MeSH terms

  • Biomarkers, Tumor / biosynthesis*
  • Bone Neoplasms / diagnosis
  • Bone Neoplasms / metabolism*
  • Bone Neoplasms / pathology
  • Cell Line, Tumor
  • Humans
  • Intracellular Signaling Peptides and Proteins / biosynthesis*
  • MicroRNAs / biosynthesis*
  • Neoplasm Proteins / biosynthesis*
  • Nerve Tissue Proteins / biosynthesis*
  • Osteosarcoma / diagnosis
  • Osteosarcoma / metabolism*
  • Osteosarcoma / pathology
  • Prognosis
  • RNA, Neoplasm / biosynthesis*

Substances

  • Biomarkers, Tumor
  • Intracellular Signaling Peptides and Proteins
  • MIRN487 microRNA, human
  • MicroRNAs
  • Neoplasm Proteins
  • Nerve Tissue Proteins
  • RNA, Neoplasm
  • TRAK2 protein, human