1. The knockdown of H19lncRNA reveals its regulatory role in pluripotency and tumorigenesis of human embryonic carcinoma cells
- Author
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Or Levkovitch, Eithan Galun, Evelyne Zeira, Zohar Bromberg, Revital Adar, Yaniv Gil, Nathalie Nahmansson, Benjamin Reubinoff, Michal Gropp, Karen Meir, Baruch Bulvik, Sharona Even Ram, and Rinat Abramovitch
- Subjects
Homeobox protein NANOG ,Pluripotent Stem Cells ,Rex1 ,Blotting, Western ,Mice, SCID ,Biology ,medicine.disease_cause ,Transfection ,Polymerase Chain Reaction ,Mice ,oncogenesis ,Cell Line, Tumor ,medicine ,Animals ,Humans ,RNA, Small Interfering ,Induced pluripotent stem cell ,H19lncRNA ,Cell potency ,Embryonic Stem Cells ,Gene knockdown ,pluripotency ,Embryonic stem cell ,Immunohistochemistry ,female genital diseases and pregnancy complications ,Cell biology ,Cell Transformation, Neoplastic ,Oncology ,Microscopy, Fluorescence ,Gene Knockdown Techniques ,embryonic structures ,Cancer research ,Heterografts ,RNA, Long Noncoding ,Carcinogenesis ,hEC cells ,Research Paper - Abstract
// Evelyne Zeira 1 , Rinat Abramovitch 1 , Karen Meir 2 , Sharona Even Ram 1,3 , Yaniv Gil 1,3 , Baruch Bulvik 1 , Zohar Bromberg 1 , Or Levkovitch 1 , Nathalie Nahmansson 1 , Revital Adar 1 , Benjamin Reubinoff 1,3 , Eithan Galun 1,* and Michal Gropp 1,3,* 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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- 2015