MiR-199b-5p promotes malignant progression of osteosarcoma by regulating HER2

J BUON. 2018 Nov-Dec;23(6):1816-1824.

Abstract

Purpose: MicroRNAs (miRs) are endogenous, noncoding small RNAs that play a key role in regulating biological and pathological processes. The oncogenic properties of miR-199b-5p have been demonstrated in previous studies but the effect of miR-199b-5p on osteosarcoma (OS) has not yet been clarified. This study aimed to investigate the effect of miR-199b-5p on OS and the relationship between this miR and the pathological parameters and prognosis of OS.

Methods: MiR-199b-5p expression in 57 pairs of OS tissues, corresponding adjacent normal tissues and OS cells was measured by quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR).The relationship between miR-199b-5p and the pathological features and prognosis of OS patients was examined. We constructed small interfering (si) RNA to knock down miR-199b-5p expression in OS cell lines MG63 and U2OS. Cell Counting Kit-8 (CCK-8), cell cloning assay and Transwell cell migration and invasion assay were applied for investigating the biological function of miR-199b-5p, respectively. Finally, western blot was used for exploring its underlying mechanism.

Results: MiR-199b-5p expression in OS was significantly higher than that of normal tissues. Compared to patients w\sith low expression of miR-199b-5p, patients with high expression level tended to be with younger age, higher incidence of distant metastases and lower overall survival. Compared with interference sequence negative control (si-NC) group, the abilities of proliferation, invasion and metastasis of cells transfected with si-miR-199b-5p were significantly decreased. Western blot analysis indicated that expressions of key proteins related to epithelial to mesenchymal transition (EMT) signaling pathway, including N-cadherin, Vimentin, β-catenin and matrix metalloproteinase-9 (MMP9), were significantly decreased after transfection with si-miR-199b-5p. Furthermore, we found that miR-199b-5p promoted the progression of OS mainly through regulating HER2.

Conclusions: Upregulated miR-199b-5p is significantly related with stage, distant metastasis and poor prognosis of OS. This MiR may promote progression of OS through regulating HER2.

MeSH terms

  • Adult
  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism*
  • Bone Neoplasms / genetics
  • Bone Neoplasms / metabolism
  • Bone Neoplasms / pathology*
  • Case-Control Studies
  • Cell Movement
  • Cell Proliferation
  • Disease Progression
  • Epithelial-Mesenchymal Transition
  • Female
  • Follow-Up Studies
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Male
  • MicroRNAs / genetics*
  • Neoplasm Invasiveness
  • Neoplasm Metastasis
  • Osteosarcoma / genetics
  • Osteosarcoma / metabolism
  • Osteosarcoma / secondary*
  • Prognosis
  • Receptor, ErbB-2 / genetics
  • Receptor, ErbB-2 / metabolism*
  • Signal Transduction
  • Survival Rate
  • Young Adult

Substances

  • Biomarkers, Tumor
  • MicroRNAs
  • mirn199 microRNA, human
  • ERBB2 protein, human
  • Receptor, ErbB-2