TY - JOUR
T1 - The knockdown of H19lncRNA reveals its regulatory role in pluripotency and tumorigenesis of human embryonic carcinoma cells
AU - Zeira, Evelyne
AU - Abramovitch, Rinat
AU - Meir, Karen
AU - Ram, Sharona Even
AU - Gil, Yaniv
AU - Bulvik, Baruch
AU - Bromberg, Zohar
AU - Levkovitch, Or
AU - Nahmansson, Nathalie
AU - Adar, Revital
AU - Reubinoff, Benjamin
AU - Galun, Eithan
AU - Gropp, Michal
PY - 2015
Y1 - 2015
N2 - 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.
AB - 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.
KW - H19lncRNA
KW - HEC cells
KW - Oncogenesis
KW - Pluripotency
UR - http://www.scopus.com/inward/record.url?scp=84946605500&partnerID=8YFLogxK
U2 - 10.18632/oncotarget.5787
DO - 10.18632/oncotarget.5787
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C2 - 26415227
AN - SCOPUS:84946605500
SN - 1949-2553
VL - 6
SP - 34691
EP - 34703
JO - Oncotarget
JF - Oncotarget
IS - 33
ER -
