title: The knockdown of H19lncRNA reveals its regulatory role in pluripotency and tumorigenesis of human embryonic carcinoma cells.
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.
authors.affiliation: The Goldyne Savad Institute of Gene Therapy, Hadassah Hebrew University Medical Center, Jerusalem, Israel.
authors.forename: Evelyne
authors.initials: E
authors.lastname: Zeira
authors.affiliation: The Goldyne Savad Institute of Gene Therapy, Hadassah Hebrew University Medical Center, Jerusalem, Israel.
authors.forename: Rinat
authors.initials: R
authors.lastname: Abramovitch
authors.affiliation: The Department of Pathology, Hadassah University Hospital, Jerusalem, Israel.
authors.forename: Karen
authors.initials: K
authors.lastname: Meir
authors.affiliation: The Goldyne Savad Institute of Gene Therapy, Hadassah Hebrew University Medical Center, Jerusalem, Israel.|The Sydney and Judy Swartz Human Embryonic Stem Cell Research Center, Hadassah-Hebrew University Medical Center, Jerusalem, Israel.
authors.forename: Sharona
authors.initials: S
authors.lastname: Even Ram
authors.affiliation: The Goldyne Savad Institute of Gene Therapy, Hadassah Hebrew University Medical Center, Jerusalem, Israel.|The Sydney and Judy Swartz Human Embryonic Stem Cell Research Center, Hadassah-Hebrew University Medical Center, Jerusalem, Israel.
authors.forename: Yaniv
authors.initials: Y
authors.lastname: Gil
authors.affiliation: The Goldyne Savad Institute of Gene Therapy, Hadassah Hebrew University Medical Center, Jerusalem, Israel.
authors.forename: Baruch
authors.initials: B
authors.lastname: Bulvik
authors.affiliation: The Goldyne Savad Institute of Gene Therapy, Hadassah Hebrew University Medical Center, Jerusalem, Israel.
authors.forename: Zohar
authors.initials: Z
authors.lastname: Bromberg
authors.affiliation: The Goldyne Savad Institute of Gene Therapy, Hadassah Hebrew University Medical Center, Jerusalem, Israel.
authors.forename: Or
authors.initials: O
authors.lastname: Levkovitch
authors.affiliation: The Goldyne Savad Institute of Gene Therapy, Hadassah Hebrew University Medical Center, Jerusalem, Israel.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Nahmansson
authors.affiliation: The Goldyne Savad Institute of Gene Therapy, Hadassah Hebrew University Medical Center, Jerusalem, Israel.
authors.forename: Revital
authors.initials: R
authors.lastname: Adar
authors.affiliation: The Goldyne Savad Institute of Gene Therapy, Hadassah Hebrew University Medical Center, Jerusalem, Israel.|The Sydney and Judy Swartz Human Embryonic Stem Cell Research Center, Hadassah-Hebrew University Medical Center, Jerusalem, Israel.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Reubinoff
authors.affiliation: The Goldyne Savad Institute of Gene Therapy, Hadassah Hebrew University Medical Center, Jerusalem, Israel.
authors.forename: Eithan
authors.initials: E
authors.lastname: Galun
authors.affiliation: The Goldyne Savad Institute of Gene Therapy, Hadassah Hebrew University Medical Center, Jerusalem, Israel.|The Sydney and Judy Swartz Human Embryonic Stem Cell Research Center, Hadassah-Hebrew University Medical Center, Jerusalem, Israel.
authors.forename: Michal
authors.initials: M
authors.lastname: Gropp
mesh_terms: D000818:Animals; D015153:Blotting, Western; D045744:Cell Line, Tumor; D002471:Cell Transformation, Neoplastic / Q000235:genetics*; D053595:Embryonic Stem Cells; D055785:Gene Knockdown Techniques; D064593:Heterografts; D006801:Humans; D007150:Immunohistochemistry; D051379:Mice; D016513:Mice, SCID; D008856:Microscopy, Fluorescence; D039904:Pluripotent Stem Cells; D016133:Polymerase Chain Reaction; D062085:RNA, Long Noncoding / Q000235:genetics*; D034741:RNA, Small Interfering; D014162:Transfection
chemical_list: C094335:H19 long non-coding RNA; D062085:RNA, Long Noncoding; D034741:RNA, Small Interfering
keywords: H19lncRNA; hEC cells; oncogenesis; pluripotency