The MicroRNA and MessengerRNA Profile of the RNA-Induced Silencing Complex in Human Primary Astrocyte and Astrocytoma CellsReportar como inadecuado




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Background

GW-P bodies are cytoplasmic ribonucleoprotein-rich foci involved in microRNA miRNA-mediated messenger RNA mRNA silencing and degradation. The mRNA regulatory functions within GW-P bodies are mediated by GW182 and its binding partner hAgo2 that bind miRNA in the RNA-induced silencing complex RISC. To date there are no published reports of the profile of miRNA and mRNA targeted to the RISC or a comparison of the RISC-specific miRNA-mRNA profile differences in malignant and non-malignant cells.

Methodology-Principal Findings

RISC mRNA and miRNA components were profiled by microarray analysis of malignant human U-87 astrocytoma cells and its non-malignant counterpart, primary human astrocytes. Total cell RNA as well as RNA from immunoprecipitated RISC was analyzed. The novel findings were fourfold: 1 miRNAs were highly enriched in astrocyte RISC compared to U-87 astrocytoma RISC, 2 astrocytoma and primary astrocyte cells each contained unique RISC miRNA profiles as compared to their respective cellular miRNA profiles, 3 miR-195, 10b, 29b, 19b, 34a and 455-3p levels were increased and the miR-181b level was decreased in U-87 astrocytoma RISC as compared to astrocyte RISC, and 4 the RISC contained decreased levels of mRNAs in primary astrocyte and U-87 astrocytoma cells.

Conclusions-Significance

The observation that miR-34a and miR-195 levels were increased in the RISC of U-87 astrocytoma cells suggests an oncogenic role for these miRNAs. Differential regulation of mRNAs by specific miRNAs is evidenced by the observation that three miR34a-targeted mRNAs and two miR-195-targeted mRNAs were downregulated while one miR-195-targeted mRNA was upregulated. Biological pathway analysis of RISC mRNA components suggests that the RISC plays a pivotal role in malignancy and other conditions. This study points to the importance of the RISC and ultimately GW-P body composition and function in miRNA and mRNA deregulation in astrocytoma cells and possibly in other malignancies.



Autor: Joanna J. Moser, Marvin J. Fritzler

Fuente: http://plos.srce.hr/



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