title: Polyploidization of murine mesenchymal cells is associated with suppression of the long noncoding RNA H19 and reduced tumorigenicity.
abstract: Mesenchymal stromal cells (MSC) are used extensively in clinical trials; however, the possibility that MSCs have a potential for malignant transformation was raised. We examined the genomic stability versus the tumor-forming capacity of multiple mouse MSCs. Murine MSCs have been shown to be less stable and more prone to malignant transformation than their human counterparts. A large series of independently isolated MSC populations exhibited low tumorigenic potential under syngeneic conditions, which increased in immunocompromised animals. Unexpectedly, higher ploidy correlated with reduced tumor-forming capacity. Furthermore, in both cultured MSCs and primary hepatocytes, polyploidization was associated with a dramatic decrease in the expression of the long noncoding RNA H19. Direct knockdown of H19 expression in diploid cells resulted in acquisition of polyploid cell traits. Moreover, artificial tetraploidization of diploid cancer cells led to a reduction of H19 levels, as well as to an attenuation of the tumorigenic potential. Polyploidy might therefore serve as a protective mechanism aimed at reducing malignant transformation through the involvement of the H19 regulatory long noncoding RNA.
authors.affiliation: Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Israel.
authors.forename: Ofer
authors.initials: O
authors.lastname: Shoshani
authors.forename: Hassan
authors.initials: H
authors.lastname: Massalha
authors.forename: Nir
authors.initials: N
authors.lastname: Shani
authors.forename: Sivan
authors.initials: S
authors.lastname: Kagan
authors.forename: Orly
authors.initials: O
authors.lastname: Ravid
authors.forename: Shalom
authors.initials: S
authors.lastname: Madar
authors.forename: Luba
authors.initials: L
authors.lastname: Trakhtenbrot
authors.forename: Dena
authors.initials: D
authors.lastname: Leshkowitz
authors.forename: Gideon
authors.initials: G
authors.lastname: Rechavi
authors.forename: Dov
authors.initials: D
authors.lastname: Zipori
mesh_terms: D000818:Animals; D002471:Cell Transformation, Neoplastic / Q000235:genetics* / Q000473:pathology; D002478:Cells, Cultured; D020868:Gene Silencing / Q000502:physiology*; D042822:Genomic Instability; D059630:Mesenchymal Stem Cells / Q000378:metabolism* / Q000473:pathology* / Q000502:physiology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D016688:Mice, Inbred NOD; D018345:Mice, Knockout; D016513:Mice, SCID; D009369:Neoplasms / Q000235:genetics; D011123:Polyploidy; D062085:RNA, Long Noncoding / Q000037:antagonists & inhibitors / Q000235:genetics*
chemical_list: C094335:H19 long non-coding RNA; D062085:RNA, Long Noncoding