MicroRNA-301a inhibits the progression of osteosarcoma by regulating DEC2

J BUON. 2020 Mar-Apr;25(2):1013-1021.

Abstract

Purpose: The purpose of this study was to investigate the expression of microRNA (miRNA)-301a in osteosarcoma (OS) and its relationship with clinicopathological parameters and prognosis of patients with OS, and to further explore how it accelerates the progression of OS via modulating downstream target genes.

Methods: Quantitative real-time polymerase chain reaction (qRT-PCR) was used to examine the expression of miRNA-301a in 39 OS tumor tissue samples and adjacent ones, and the interplay between miRNA-301a and clinical indicators. The prognosis of patients with OS was analyzed. In addition, miRNA-301a overexpression vector was constructed to analyze the effect of miRNA-301a on the function of OS cells by cell counting kit-8 (CCK-8), transwell and cell wound healing assays. Finally, the potential mechanism was also investigated using luciferase reporter gene assay and cell recovery experiment.

Results: qRT-PCR results revealed that miRNA-301a level in OS tumor tissue specimen was remarkably lower than that in adjacent tissue. Compared with patients with high expression of miRNA-301a, patients with low expression had a higher incidence of distant metastasis and lower overall survival. Compared with the negative control group (miR-NC group), cell proliferation and metastasis ability were remarkably decreased in the miRNA-301a mimics group. In addition, DEC2 expression was found remarkably elevated in OS cell lines and negatively correlated with miRNA-301a level. At the same time, cell recovery experiment demonstrated that there existed a mutual regulation between miRNA-301a and DEC2, the two of which could together promote the malignant progression of OS.

Conclusions: MiRNA-301a level was remarkably reduced both in OS tissues and cell line samples, and was confirmed to be associated with distant metastasis and poor prognosis of patients with OS. In addition, miRNA-301a was found to be able to inhibit malignant progression of OS through regulating DEC2.

MeSH terms

  • Adult
  • Basic Helix-Loop-Helix Transcription Factors / genetics*
  • Bone Neoplasms / genetics*
  • Bone Neoplasms / metabolism*
  • Bone Neoplasms / pathology
  • Cell Line, Tumor
  • Disease Progression
  • Female
  • Humans
  • Male
  • MicroRNAs / biosynthesis
  • MicroRNAs / genetics*
  • MicroRNAs / metabolism
  • Osteosarcoma / genetics*
  • Osteosarcoma / metabolism*
  • Osteosarcoma / pathology
  • Transfection
  • Young Adult

Substances

  • BHLHE41 protein, human
  • Basic Helix-Loop-Helix Transcription Factors
  • MIRN301A microRNA, human
  • MicroRNAs