This project contains all information pertaining to the replication of key experiments from this paper. It includes the detailed protocols, including reagents and author clarifications. We also include any comments from other contributors, researchers from the Science Exchange network, and further information with the original authors that we have learned since the beginning of the project. When experimental studies begin all data collected will also be deposited here, including data analysis and eventually the final written report.
<br>
**Original citation:**
Sumazin P., Yang X., Chiu H.-S., Chung W.-J., Iyer A., Llobet-Navas D., Rajbhandari P., Bansal M., Guarnieri P., Silva J., Califano A. An Extensive MicroRNA-Mediated Network of RNA-RNA Interactions Regulates Established Oncogenic Pathways in Glioblastoma. Cell. 2011 Oct 14;147(2):370-81. doi: 10.1016/j.cell.2011.09.041.
<br>
**Original paper abstract:**
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 similar to 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 PTEN, PDGFRA, RB1, VEGFA, STAT3, 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 of PTEN expression variability, was sufficient to downregulate PTEN in a 30UTR-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.
