Argonaute-miRNA complexes reveal concerted action in disease related pathways of a human, glioblastoma cell line

Glioblastoma is the most common primary malignant brain tumor occurring in the central nervous system and is characterized by rapid proliferation, genetic aberrations and poor response to treatment. The classical genetic alterations in glioblastoma target pathways governing cellular proliferation, cellular survival, invasion and angiogenesis. In this study, the regulation of glioblastoma-relevant pathways by small non-coding RNAs was analyzed by identification of Argonaute protein-associated microRNAs and mRNAs. We utilized a highly controlled method termed PAR-CLIP-Array by biochemical isolation of cross-linked ribonucleoprotein complexes with monoclonal antibodies specific for individual Argonaute proteins followed by microarray detection. We demonstrate here that the different Argonaute proteins bind different subsets of miRNAs and mRNAs in a glioblastoma cell line model. By extending our study generating miRNA-mRNA network interaction models we could further show, that different Argonaute proteins act in concert to regulate glioblastoma-relevant pathways. We therefore provide novel insights into glioblastoma regulation by microRNAs.

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