The knockdown of H19lncRNA reveals its regulatory role in pluripotency and tumorigenesis of human embryonic carcinoma cells

  • Evelyne Zeira
  • , Rinat Abramovitch
  • , Karen Meir
  • , Sharona Even Ram
  • , Yaniv Gil
  • , Baruch Bulvik
  • , Zohar Bromberg
  • , Or Levkovitch
  • , Nathalie Nahmansson
  • , Revital Adar
  • , Benjamin Reubinoff
  • , Eithan Galun
  • , Michal Gropp*
  • *Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

23 Scopus citations

Abstract

The function of imprinted H19 long non-coding RNA is still controversial. It is highly expressed in early embryogenesis and decreases after birth and re-expressed in cancer. To study the role of H19 in oncogenesis and pluripotency, we down-regulated H19 expression in vitro and in vivo in pluripotent human embryonic carcinoma (hEC) and embryonic stem (hES) cells. H19 knockdown resulted in a decrease in the expression of the pluripotency markers Oct4, Nanog, TRA-1-60 and TRA-1-81, and in the up-regulation of SSEA1; it further attenuated cell proliferation, decreased cell-matrix attachment, and up-regulated E-Cadherin expression. SCID-Beige mice transplanted with H19 down-regulated hEC cells exhibited slower kinetics of tumor formation, resulting in an increased animal survival. Tumors derived from H19 down-regulated cells showed a decrease in the expression of pluripotency markers and up-regulation of SSEA-1 and E-cadherin. Our results suggest that H19 oncogenicity in hEC cells is mediated through the regulation of the pluripotency state.

Original languageEnglish
Pages (from-to)34691-34703
Number of pages13
JournalOncotarget
Volume6
Issue number33
DOIs
StatePublished - 2015
Externally publishedYes

Keywords

  • H19lncRNA
  • HEC cells
  • Oncogenesis
  • Pluripotency

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