"The mind is a compact, multiply connected thought mass with internal connections of the most intimate kind. It grows continuously as new thought masses enter it, and this is the means by which it continues to develop."

Bernhard Riemann On Psychology and Metaphysics ca. 1860

Today's Elites


Saturday, October 15, 2011

Micro RNAs and Biophysics Methodology

This research is indicative of the continuing overturning of dogma regarding simple point mutation of genes and disease. I wrote here in 2009 that the complex interaction of a protein multi functional network was reminiscent of a Riemann surface branch point function. The further discovery of the functional network of RNA/DNA interactions adds to this perspective:


Interactions Regulates Established Oncogenic Pathways in Glioblastoma

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Cell, Volume 147, Issue 2, 370-381, 14 October 2011
Copyright © 2011 Elsevier Inc. All rights reserved.
10.1016/j.cell.2011.09.041

Authors

  • Highlights
  • Computational inference reveals a network of miR-mediated interactions in glioblastoma
  • These interactions regulate thousands of genes, including oncogenes and tumor suppressors
  • These interactions regulate miR targets without affecting miR expression
  • These interactions enable crosstalk between established oncogenic pathways

Summary

By analyzing gene expression data in glioblastoma in combination with matched microRNA profiles, we have uncovered a posttranscriptional regulation layer of surprising magnitude, comprising more than 248,000 microRNA (miR)-mediated interactions. These include ∼7,000 genes whose transcripts act as miR “sponges” and 148 genes that act through alternative, nonsponge interactions. Biochemical analyses in cell lines confirmed that this network regulates established drivers of tumor initiation and subtype implementation, including PTENPDGFRARB1VEGFASTAT3, and RUNX1, suggesting that these interactions mediate crosstalk between canonical oncogenic pathways. siRNA silencing of 13 miR-mediated PTEN regulators, whose locus deletions are predictive ofPTEN expression variability, was sufficient to downregulate PTEN in a 3′UTR-dependent manner and to increase tumor cell growth rates. Thus, miR-mediated interactions provide a mechanistic, experimentally validated rationale for the loss of PTEN expression in a large number of glioma samples with an intact PTEN locus.

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