Oncotarget

Research Papers:

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 and Michal Gropp _

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Oncotarget. 2015; 6:34691-34703. https://doi.org/10.18632/oncotarget.5787

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Abstract

Evelyne Zeira1, Rinat Abramovitch1, Karen Meir2, Sharona Even Ram1,3, Yaniv Gil1,3, Baruch Bulvik1, Zohar Bromberg1, Or Levkovitch1, Nathalie Nahmansson1, Revital Adar1, Benjamin Reubinoff1,3, Eithan Galun1,* and Michal Gropp1,3,*

1 The Goldyne Savad Institute of Gene Therapy, Hadassah Hebrew University Medical Center, Jerusalem, Israel

2 The Department of Pathology, Hadassah University Hospital, Jerusalem, Israel

3 The Sydney and Judy Swartz Human Embryonic Stem Cell Research Center, Hadassah-Hebrew University Medical Center, Jerusalem, Israel

* These authors have contributed equally to this work

Correspondence to:

Michal Gropp, email:

Eithan Galun, email:

Keywords: H19lncRNA, oncogenesis, pluripotency, hEC cells

Received: August 26, 2015 Accepted: August 31, 2015 Published: September 22, 2015

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.


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