TUSC8 inhibits the development of osteosarcoma by sponging miR‑197‑3p and targeting EHD2

Int J Mol Med. 2020 Oct;46(4):1311-1320. doi: 10.3892/ijmm.2020.4684. Epub 2020 Jul 27.

Abstract

Osteosarcoma (OS) is one of the most common malignant bone tumours and generally occurs in children and adolescents. Increasing evidence has demonstrated that dysregulated long non‑coding RNAs (lncRNAs) play crucial roles in the progression of various human neoplasms. Among these, tumour suppressor candidate 8 (TUSC8) is a novel lncRNA and has been reported to function as a tumour suppressor in cervical cancer. However, the exact role of TUSC8 in OS remains largely unknown. In the present study, it was observed that TUSC8 was markedly downregulated in OS tissues and cell lines. Functional experiments demonstrated that the overexpression of TUSC8 significantly suppressed the proliferation, migration, invasion and epithelial‑mesenchymal transition (EMT), whereas it accelerated the apoptosis of OS cells. Mechanistically, TUSC8 served as a sponge for miR‑197‑3p, and EH‑domain containing 2 (EHD2) was identified as a downstream target molecule of miR‑197‑3p. Further investigations indicated that EHD2 knockdown significantly reversed the effects on OS cellular processes induced by TUSC8 overexpression. On the whole, these findings indicate that TUSC8 functions as a competing endogenous RNA (ceRNA) to suppress OS cell growth and EMT via the miR‑197‑3p/EHD2 axis. TUSC8 may thus function as a potential therapeutic target in OS treatment.

MeSH terms

  • Apoptosis / genetics
  • Bone Neoplasms / genetics*
  • Bone Neoplasms / pathology
  • Carrier Proteins / genetics*
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Proliferation / genetics
  • Epithelial-Mesenchymal Transition / genetics
  • Gene Expression Regulation, Neoplastic / genetics
  • Humans
  • MicroRNAs / genetics*
  • Osteosarcoma / genetics*
  • Osteosarcoma / pathology
  • RNA, Long Noncoding / genetics*

Substances

  • Carrier Proteins
  • EHD2 protein, human
  • MIRN197 microRNA, human
  • MicroRNAs
  • RNA, Long Noncoding
  • TUSC8 long non-coding RNA, human