Cargando…

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

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...

Descripción completa

Detalles Bibliográficos
Autores principales: Zeira, Evelyne, Abramovitch, Rinat, Meir, Karen, Ram, Sharona Even, Gil, Yaniv, Bulvik, Baruch, Bromberg, Zohar, Levkovitch, Or, Nahmansson, Nathalie, Adar, Revital, Reubinoff, Benjamin, Galun, Eithan, Gropp, Michal
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals LLC 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4741483/
https://www.ncbi.nlm.nih.gov/pubmed/26415227
_version_ 1782414001417748480
author Zeira, Evelyne
Abramovitch, Rinat
Meir, Karen
Ram, Sharona Even
Gil, Yaniv
Bulvik, Baruch
Bromberg, Zohar
Levkovitch, Or
Nahmansson, Nathalie
Adar, Revital
Reubinoff, Benjamin
Galun, Eithan
Gropp, Michal
author_facet Zeira, Evelyne
Abramovitch, Rinat
Meir, Karen
Ram, Sharona Even
Gil, Yaniv
Bulvik, Baruch
Bromberg, Zohar
Levkovitch, Or
Nahmansson, Nathalie
Adar, Revital
Reubinoff, Benjamin
Galun, Eithan
Gropp, Michal
author_sort Zeira, Evelyne
collection PubMed
description 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.
format Online
Article
Text
id pubmed-4741483
institution National Center for Biotechnology Information
language English
publishDate 2015
publisher Impact Journals LLC
record_format MEDLINE/PubMed
spelling pubmed-47414832016-03-15 The knockdown of H19lncRNA reveals its regulatory role in pluripotency and tumorigenesis of human embryonic carcinoma cells Zeira, Evelyne Abramovitch, Rinat Meir, Karen Ram, Sharona Even Gil, Yaniv Bulvik, Baruch Bromberg, Zohar Levkovitch, Or Nahmansson, Nathalie Adar, Revital Reubinoff, Benjamin Galun, Eithan Gropp, Michal Oncotarget Research Paper 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. Impact Journals LLC 2015-09-22 /pmc/articles/PMC4741483/ /pubmed/26415227 Text en Copyright: © 2015 Zeira et al. http://creativecommons.org/licenses/by/2.5/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Paper
Zeira, Evelyne
Abramovitch, Rinat
Meir, Karen
Ram, Sharona Even
Gil, Yaniv
Bulvik, Baruch
Bromberg, Zohar
Levkovitch, Or
Nahmansson, Nathalie
Adar, Revital
Reubinoff, Benjamin
Galun, Eithan
Gropp, Michal
The knockdown of H19lncRNA reveals its regulatory role in pluripotency and tumorigenesis of human embryonic carcinoma cells
title The knockdown of H19lncRNA reveals its regulatory role in pluripotency and tumorigenesis of human embryonic carcinoma cells
title_full The knockdown of H19lncRNA reveals its regulatory role in pluripotency and tumorigenesis of human embryonic carcinoma cells
title_fullStr The knockdown of H19lncRNA reveals its regulatory role in pluripotency and tumorigenesis of human embryonic carcinoma cells
title_full_unstemmed The knockdown of H19lncRNA reveals its regulatory role in pluripotency and tumorigenesis of human embryonic carcinoma cells
title_short The knockdown of H19lncRNA reveals its regulatory role in pluripotency and tumorigenesis of human embryonic carcinoma cells
title_sort knockdown of h19lncrna reveals its regulatory role in pluripotency and tumorigenesis of human embryonic carcinoma cells
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4741483/
https://www.ncbi.nlm.nih.gov/pubmed/26415227
work_keys_str_mv AT zeiraevelyne theknockdownofh19lncrnarevealsitsregulatoryroleinpluripotencyandtumorigenesisofhumanembryoniccarcinomacells
AT abramovitchrinat theknockdownofh19lncrnarevealsitsregulatoryroleinpluripotencyandtumorigenesisofhumanembryoniccarcinomacells
AT meirkaren theknockdownofh19lncrnarevealsitsregulatoryroleinpluripotencyandtumorigenesisofhumanembryoniccarcinomacells
AT ramsharonaeven theknockdownofh19lncrnarevealsitsregulatoryroleinpluripotencyandtumorigenesisofhumanembryoniccarcinomacells
AT gilyaniv theknockdownofh19lncrnarevealsitsregulatoryroleinpluripotencyandtumorigenesisofhumanembryoniccarcinomacells
AT bulvikbaruch theknockdownofh19lncrnarevealsitsregulatoryroleinpluripotencyandtumorigenesisofhumanembryoniccarcinomacells
AT brombergzohar theknockdownofh19lncrnarevealsitsregulatoryroleinpluripotencyandtumorigenesisofhumanembryoniccarcinomacells
AT levkovitchor theknockdownofh19lncrnarevealsitsregulatoryroleinpluripotencyandtumorigenesisofhumanembryoniccarcinomacells
AT nahmanssonnathalie theknockdownofh19lncrnarevealsitsregulatoryroleinpluripotencyandtumorigenesisofhumanembryoniccarcinomacells
AT adarrevital theknockdownofh19lncrnarevealsitsregulatoryroleinpluripotencyandtumorigenesisofhumanembryoniccarcinomacells
AT reubinoffbenjamin theknockdownofh19lncrnarevealsitsregulatoryroleinpluripotencyandtumorigenesisofhumanembryoniccarcinomacells
AT galuneithan theknockdownofh19lncrnarevealsitsregulatoryroleinpluripotencyandtumorigenesisofhumanembryoniccarcinomacells
AT groppmichal theknockdownofh19lncrnarevealsitsregulatoryroleinpluripotencyandtumorigenesisofhumanembryoniccarcinomacells
AT zeiraevelyne knockdownofh19lncrnarevealsitsregulatoryroleinpluripotencyandtumorigenesisofhumanembryoniccarcinomacells
AT abramovitchrinat knockdownofh19lncrnarevealsitsregulatoryroleinpluripotencyandtumorigenesisofhumanembryoniccarcinomacells
AT meirkaren knockdownofh19lncrnarevealsitsregulatoryroleinpluripotencyandtumorigenesisofhumanembryoniccarcinomacells
AT ramsharonaeven knockdownofh19lncrnarevealsitsregulatoryroleinpluripotencyandtumorigenesisofhumanembryoniccarcinomacells
AT gilyaniv knockdownofh19lncrnarevealsitsregulatoryroleinpluripotencyandtumorigenesisofhumanembryoniccarcinomacells
AT bulvikbaruch knockdownofh19lncrnarevealsitsregulatoryroleinpluripotencyandtumorigenesisofhumanembryoniccarcinomacells
AT brombergzohar knockdownofh19lncrnarevealsitsregulatoryroleinpluripotencyandtumorigenesisofhumanembryoniccarcinomacells
AT levkovitchor knockdownofh19lncrnarevealsitsregulatoryroleinpluripotencyandtumorigenesisofhumanembryoniccarcinomacells
AT nahmanssonnathalie knockdownofh19lncrnarevealsitsregulatoryroleinpluripotencyandtumorigenesisofhumanembryoniccarcinomacells
AT adarrevital knockdownofh19lncrnarevealsitsregulatoryroleinpluripotencyandtumorigenesisofhumanembryoniccarcinomacells
AT reubinoffbenjamin knockdownofh19lncrnarevealsitsregulatoryroleinpluripotencyandtumorigenesisofhumanembryoniccarcinomacells
AT galuneithan knockdownofh19lncrnarevealsitsregulatoryroleinpluripotencyandtumorigenesisofhumanembryoniccarcinomacells
AT groppmichal knockdownofh19lncrnarevealsitsregulatoryroleinpluripotencyandtumorigenesisofhumanembryoniccarcinomacells