The knockdown of H19lncRNA reveals its regulatory role in pluripotency and tumorigenesis of human embryonic carcinoma cells
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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
Michal Gropp, email:
Eithan Galun, email:
Keywords: H19lncRNA, oncogenesis, pluripotency, hEC cells
Received: August 26, 2015 Accepted: August 31, 2015 Published: September 22, 2015
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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