Tissue Elasticity Regulated Tumor Gene Expression: Implication for Diagnostic Biomarkers of Primitive XXXX .

@entity1 @entity852 @entity4969 @entity5 @entity310 @entity7433 @entity3880 @entity14315 @entity2975 @entity6474
BACKGROUND: The @entity5 microenvironment consists of both physical and chemical factors. Tissue elasticity is one physical factor contributing to the microenvironment of @entity5 cells. To test the importance of tissue elasticity in cell culture, primitive @entity4969 (PNET) stem cells were cultured on soft @entity2975 ( @entity3880 ) hydrogel plates that mimics the elasticity of brain tissue compared with PNET on standard @entity852 (PS) plates. We report the molecular profiles of PNET grown on either @entity3880 or PS. METHODOLOGY/PRINCIPAL FINDINGS: A whole-genome microarray profile of transcriptional expression between the two culture conditions was performed as a way to probe effects of substrate on cell behavior in culture. The results showed more genes downregulated on @entity3880 compared to PS. This led us to propose microRNA (miRNA) silencing as a potential mechanism for downregulation. Bioinformatic analysis predicted a greater number of miRNA binding sites from the 3' UTR of downregulated genes and identified as specific miRNA binding sites that were enriched when cells were grown on @entity3880 -this supports the hypothesis that tissue elasticity plays a role in influencing miRNA expression. Thus, Dicer was examined to determine if miRNA processing was affected by tissue elasticity. Dicer genes were downregulated on @entity3880 and had multiple predicted miRNA binding sites in its 3' UTR that matched the miRNA binding sites found enriched on @entity3880 . Many differentially regulated genes were found to be present on PS but downregulated on @entity3880 were mapped onto intron sequences. This suggests expression of alternative polyadenylation sites within intron regions that provide alternative 3' UTRs and alternative miRNA binding sites. This results in tissue specific transcriptional downregulation of mRNA in @entity1 by miRNA. We propose a mechanism, driven by the physical characteristics of the microenvironment by which downregulation of genes occur. We found that tissue elasticity-mediated cytokines ( @entity6474 and @entity310 ) signaling affect expression of @entity14315 proteins. CONCLUSIONS: Our results suggest that tissue elasticity plays important roles in miRNA expression, which, in turn, regulate @entity5 growth or @entity7433 .
