4.6 Article

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

Journal

Publisher

ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.bbrc.2018.04.019

Keywords

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

Funding

  1. Nature Science Foundation of Zhejiang Province [LY18H060013]
  2. Foundation of Zhejiang Province medical health [2016RCA029, 2018KY820]
  3. Medical and Health Research Project of Zhejiang, Province [2017KY662, 2018KY825]
  4. science and technology project of Shaoxing [2017CX007]

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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 (1GF2BP1) 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. (C) 2018 Elsevier Inc. All rights reserved.

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