Long Noncoding MT1JP Enhanced the Inhibitory Effects of miR-646 on FGF2 in Osteosarcoma

Cancer Biother Radiopharm. 2020 Jun;35(5):371-376. doi: 10.1089/cbr.2019.3328. Epub 2020 Mar 20.

Abstract

Background: It has been reported that long noncoding RNA (lncRNA) MT1JP played a tumor-suppressive role in the development of many organs, such as liver and lung, but the exact mechanism is still unknown. In addition, the involvement of MT1JP in osteosarcoma (OS) and its clinical values are unknown. In this study, the authors explored the interactions among lncRNA MT1JP, miR-646, and FOXK1 in OS. Materials and Methods: Expression levels of MT1JP in both tumor and nontumor tissues from 42 early stage OS patients were measured by reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Plasma levels of MT1JP in both OS patients (n = 42) and healthy controls (n = 42) were also measured by RT-qPCR. ROC curve as used for diagnostic analysis. Overexpression experiments were performed to analyze the interaction among MT1JP, miR-646, and FGF2. Cell invasion and migration were analyzed by Transwell assays. Results: The authors found that MT1JP was significantly downregulated in OS tissues than in adjacent noncancer tissues. In addition, plasma MT1JP was also downregulated in OS patients than in healthy controls. The lower plasma levels of MT1JP in OS patients distinguished early stage OS patients from healthy controls. miR-646 was positive, but FGF2 was negatively correlated with MT1JP across OS tissues. The MT1JP overexpression upregulated miR-646 and downregulated FGF2, while the miR-646 overexpression downregulated FGF2, but showed no significant effects on the MT1JP expression. MT1JP and miR-646 overexpression inhibited the migration and invasion of OS cells. The FGF2 overexpression played the opposite role and attenuated the effects of MT1JP and miR-646 overexpression. Conclusions: In conclusion, MT1JP might downregulate FGF2 through miR-646 to inhibit OS cell migration and invasion. The downregulation of plasma circulating MT1JP may serve as an early diagnostic biomarker for OS.

Keywords: FGF2; lncRNA MT1JP; miR-646; osteosarcoma.

Publication types

  • Observational Study

MeSH terms

  • Adolescent
  • Adult
  • Biomarkers, Tumor / blood
  • Biomarkers, Tumor / metabolism
  • Biopsy
  • Bone Neoplasms / blood
  • Bone Neoplasms / diagnosis
  • Bone Neoplasms / genetics*
  • Bone Neoplasms / pathology
  • Bone and Bones / pathology
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell-Free Nucleic Acids / blood
  • Cell-Free Nucleic Acids / metabolism
  • Down-Regulation
  • Fibroblast Growth Factor 2 / genetics*
  • Humans
  • Male
  • MicroRNAs / metabolism*
  • Neoplasm Invasiveness / genetics
  • Neoplasm Staging
  • Osteosarcoma / blood
  • Osteosarcoma / diagnosis
  • Osteosarcoma / genetics*
  • Osteosarcoma / pathology
  • RNA, Long Noncoding / blood
  • RNA, Long Noncoding / metabolism*
  • Young Adult

Substances

  • Biomarkers, Tumor
  • Cell-Free Nucleic Acids
  • MIRN646 microRNA, human
  • MicroRNAs
  • RNA, Long Noncoding
  • Fibroblast Growth Factor 2