RSF1 functions as an oncogene in osteosarcoma and is regulated by XIST/miR-193a-3p axis

Biomed Pharmacother. 2017 Nov:95:207-214. doi: 10.1016/j.biopha.2017.08.068. Epub 2017 Sep 12.

Abstract

RSF1 (HBXAP), is a member of ATP-dependent chromatin remodeling factor. Dysregulated RSF1 has been reported to be related to tumor progression. However, the function of RSF1 in osteosarcoma (OS) remains unclear. In this study, we showed that RSF1 expression was upregulated in OS cells. RSF1 inhibition suppressed OS cell proliferation and invasion. We further showed that MAPK/Erk signaling pathway was inactivated by RSF1 suppression. In addition, RSF1 was identified as a direct target of miR-193a-3p. Clinically, RSF1 was increased and associated with advanced clinical features and poor overall survival of OS patients. MiR-193a-3p expression was decreased and associated with advanced clinical features and poor overall survival of OS patients. In addition, we found that miR-193a-3p was negatively correlated with RSF1 expression in OS tissues. Moreover, our data showed that XIST could function as competing endogenous RNA to repress miR-193a-3p, which regulated its downstream target RSF1. In conclusion, our findings demonstrated that the XIST/miR-193a-3p/RSF1 axis might contribute to the progression and act as a therapeutic target of OS patients.

Keywords: MAPK/Erk; Osteosarcoma; RSF1; XIST; miR-193a-3p.

MeSH terms

  • Adult
  • Animals
  • Bone Neoplasms / genetics
  • Bone Neoplasms / metabolism*
  • Bone Neoplasms / mortality
  • Cell Line, Tumor
  • Female
  • HEK293 Cells
  • Humans
  • Male
  • Mice
  • Mice, Nude
  • MicroRNAs / physiology*
  • Nuclear Proteins / physiology*
  • Oncogenes / physiology*
  • Osteosarcoma / genetics
  • Osteosarcoma / metabolism*
  • Osteosarcoma / mortality
  • RNA, Long Noncoding / physiology*
  • Signal Transduction / physiology
  • Trans-Activators / physiology*
  • Xenograft Model Antitumor Assays / methods
  • Young Adult

Substances

  • MIRN193 microRNA, human
  • MicroRNAs
  • Nuclear Proteins
  • RNA, Long Noncoding
  • RSF1 protein, human
  • Trans-Activators
  • XIST non-coding RNA