Polyploidization of murine mesenchymal cells is associated with suppression of the long noncoding RNA H19 and reduced

Ofer Shoshani1, Hassan Massalha, Nir Shani

  • 1Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Israel.

Cancer Research
|October 11, 2012
PubMed

Insights

Mesenchymal stromal cells (MSCs) showed reduced tumor formation with higher ploidy. Polyploidization, linked to decreased H19 long noncoding RNA, may protect against malignant transformation.

Area of Science:

  • Cell Biology
  • Genomics
  • Cancer Research

Background:

  • Mesenchymal stromal cells (MSCs) are widely used in clinical trials.
  • Concerns exist regarding the potential for MSC malignant transformation.
  • Murine MSCs exhibit greater genomic instability than human MSCs.

Purpose of the Study:

  • To investigate the relationship between genomic stability and tumor-forming capacity in mouse MSCs.
  • To explore the role of polyploidy and H19 long noncoding RNA in MSC tumorigenesis.

Main Methods:

  • Examined genomic stability and tumor-forming capacity of multiple mouse MSC populations.
  • Assessed the correlation between cell ploidy and tumorigenic potential.
  • Investigated the expression of H19 long noncoding RNA in polyploid cells and its functional role via knockdown and artificial tetraploidization.

Main Results:

  • Mouse MSCs demonstrated low tumorigenic potential in syngeneic hosts, increasing in immunocompromised animals.
  • Higher cell ploidy unexpectedly correlated with reduced tumor-forming capacity.
  • Polyploidization in MSCs and hepatocytes was associated with decreased H19 expression.
  • H19 knockdown induced polyploid cell traits; artificial tetraploidization reduced H19 levels and tumorigenicity in cancer cells.

Conclusions:

  • Polyploidy may act as a protective mechanism against malignant transformation in MSCs.
  • The H19 long noncoding RNA is implicated in the regulatory pathway linking polyploidy to reduced tumorigenesis.

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