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

// 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.