| 研究実績の概要 |
Neuroblastoma(NB) is the most common solid tumor in infants and big cause of cancer death. NB arising from neural crest, is classified unfavorable and favorable outcome.
Recently, we compared gene expressions between favorable and unfavorable group by oligo-microarray and top hits genes were <I>DHRS3</I>, <I>NR0B1</I>, and <I>CYP26A1</I> in the favorable groups. We established overexpressing and silencing clones of five neuroblastoma cells using plasmid transfection or Retrovirus Tet-On expression system.
Of those overexpressing clones, especially SKNSH and NH12 expressing <I>DHRS3</I> represented reduced cell growth rate, inducing a G1 cell-cycle arrest, reduced colony formation ability, differentiated character within 10 days and mostly inducind cell death. We also found the ectopic expression of <I>DHRS3</I> promotes lipid droplet accumulation and that lead to cellular differentiation after TP53 activation.
Further RNA-seq analysis revealed that <I>DHRS3</I> and <I>NR0B1</I> expressing clones promotes cellular senescence and differentiation, whereas <I>CYP26A1</I> was not effective for the cellular malignancy.
So we suppose that <I>DHRS3</I> and <I>NR0B1</I> are the potential target for the treatment of neuroblastoma.
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