Long non-coding RNA THOR promotes human osteosarcoma cell growth in vitro and in vivo

Biochem Biophys Res Commun. 2018 May 23;499(4):913-919. doi: 10.1016/j.bbrc.2018.04.019. Epub 2018 Apr 9.

Abstract

Long non-coding RNA (LncRNA) dysregulation is associated with human osteosarcoma (OS) cell progression. Recent studies have characterized a novel but ultra-conserved LncRNA THOR ("Lnc-THOR") as a cancer-specific LncRNA, mediating cell growth. In the current study, we show that Lnc-THOR is expressed in established and primary human OS cells. It is also detected in human OS tissues, but not in the surrounding normal bone tissues. siRNA-induced knockdown or CRSIPR/Cas9-mediated knockout Lnc-THOR significantly inhibited human OS cell survival and proliferation. Insulin-like growth factor 2 mRNA-binding protein 1 (IGF2BP1) target mRNAs, including IGF2, GLI1 and CD44, were downregulated in Lnc-THOR-silenced OS cells as well. Conversely, forced over-expression of Lnc-THOR enhanced IGF2BP1 target mRNA expression, promoting OS cell survival and proliferation. In vivo, xenograft tumors of Lnc-THOR-knockout U2OS cells grew significantly slower than the control U2OS tumors. Together, these results show that Lnc-THOR expression is essential for human OS cell growth. Lnc-THOR could be a novel therapeutic target and/or diagnosis marker for human OS.

Keywords: Cell growth; IGF2BP1; Lnc-THOR; Long non-coding RNA; Osteosarcoma.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line, Tumor
  • Cell Proliferation / genetics
  • Cell Survival
  • Gene Expression Regulation, Neoplastic
  • Gene Knockout Techniques
  • Humans
  • Mice, SCID
  • Osteosarcoma / genetics*
  • Osteosarcoma / pathology*
  • RNA, Long Noncoding / genetics
  • RNA, Long Noncoding / metabolism*
  • RNA, Small Interfering / metabolism

Substances

  • RNA, Long Noncoding
  • RNA, Small Interfering