Circular RNA circNASP modulates the malignant behaviors in osteosarcoma via miR-1253/FOXF1 pathway

Biochem Biophys Res Commun. 2018 Jun 2;500(2):511-517. doi: 10.1016/j.bbrc.2018.04.131. Epub 2018 Apr 21.

Abstract

Increasing evidences demonstrate that circular RNAs (circRNAs) serve as essential regulators in various human diseases, including cancer. However, the study on circRNA function in osteosarcoma (OS) is just emerging. In the present study, we screened out a novel circRNA termed circNASP which was significantly upregulated in OS tissues compared to adjacent normal tissues. We found that circNASP knockdown dramatically inhibited the proliferation, cell cycle progression and invasion of OS cells. Moreover, we showed that circNASP expression was positively correlated with tumor size and metastasis in OS patients. In terms of mechanism, we found that circNASP acts as a sponge of miR-1253 targeting FOXF1 in OS cells. By inhibiting miR-1253 availability, circNASP promoted FOXF1 expression. Rescue assays indicated that inhibition of miR-1253 could significantly reverse the effects of circNASP knockdown on OS cell proliferation and invasion while restoration of FOXF1 rescued the proliferation and invasion of OS cells transfected with miR-1253 mimics. Taken together, our findings demonstrated that circNASP contributes to malignant behaviors of OS cells by miR-1253/FOXF1 pathway, which suggested circNASP/miR-1253/FOXF1axis might be a potential therapeutic target.

Keywords: Cell cycle; Invasion; Osteosarcoma; Proliferation; circNASP.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Base Sequence
  • Cell Line, Tumor
  • Cell Proliferation / genetics
  • Female
  • Forkhead Transcription Factors / genetics
  • Forkhead Transcription Factors / metabolism*
  • Gene Knockdown Techniques
  • Humans
  • Male
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Neoplasm Invasiveness
  • Osteosarcoma / genetics*
  • Osteosarcoma / pathology*
  • RNA / genetics
  • RNA / metabolism*
  • RNA, Circular
  • Signal Transduction

Substances

  • FOXF1 protein, human
  • Forkhead Transcription Factors
  • MIRN1253 microRNA, human
  • MicroRNAs
  • RNA, Circular
  • RNA