Micro RNA-125b (miRNA-125b) Function in Astrogliosis and Glial Cell Proliferation

Micro RNAs (miRNAs) are post-transcriptional modulators of gene expression that regulate the stability and translation of their target messenger RNAs (mRNAs). Here we report that the levels of a human brain-enriched miRNA-125b are up-regulated in interleukin-6 (IL-6)-stressed normal human astrocytes (NHA), a treatment known to induce astrogliosis. In vitro, anti-miRNA-125b added exogenously to IL-6-stressed NHA cultures attenuated both glial cell proliferation and increased the expression of the cyclin-dependent kinase inhibitor 2A (CDKN2A), a miRNA-125b target and negative regulator of cell growth. A strong positive correlation between miRNA-125b abundance and the glial cell markers glial fibrillary acidic protein (GFAP) and vimentin, and CDKN2A down-regulation was noted in advanced Alzheimer's disease (AD) and in Down's syndrome (DS) brain, chronic neurological disorders associated with astrogliosis. The results suggest that miRNA-125b up-regulation contributes to astrogliosis and to defects in the cell cycle that are characteristic of degenerating brain tissues.