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W. J. Lukiw, P. K. Mukherjee, J.-G. Cui, N. G. Bazan; Up-Regulation of Micro-RNA-125b (chr 11q24; chr 21q21) in Retinoic Acid-Induced, and in Aging, Retinal Pigment Epithelial (ARPE-19) Cells. Invest. Ophthalmol. Vis. Sci. 2010;51(13):4095.
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Micro RNAs (miRNAs) are potent post-transcriptional modulators of gene expression that regulate the stability and translation of their target messenger RNA (mRNA). This study examined miRNA complexity in all-trans-retinoic-acid (RA) induced, aging ARPE-19 cells, and in RA-stressed neuronal-glial co-cultures of human neural (HN) cells.
ARPE-19 cell culture; bioinformatics (Silicon Genetics, Redwood City, CA); DNA array (Affymetrix, Santa Clara, CA); Northern analysis; primary HN cell culture; retinoic acid; RT-PCR; statistical analysis; Western analysis.
A human brain cell-enriched miRNA-125b, known to be associated with cellular proliferation, neural-derived cellular differentiation, brain cell fate and survival was significantly up-regulated in all-trans RA-stressed ARPE-19 and HN cells. The up-regulation of miRNA-125b was associated with the rate of growth of ARPE-19 and HN cells, and also linked to a reduction in the expression, at both the mRNA and protein level, of the cyclin-dependent kinase inhibitor 2A (CDKN2A), a known miRNA-125b target and negative regulator of cellular proliferation.
miRNAs are powerful effectors of retinal and neural genetic signaling. A brain-enriched miRNA-125b appears to be involved in growth of ARPE-19 and primary HN cell neuronal-glial co-cultures, in part through the down-regulation of the cell cycle regulator CDKN2A. Other specific mRNA targets for miRNA-125b are currently under investigation. Pharmacotherapeutic strategies targeted at altering miRNA-125b abundance and neutralizing this small RNA’s pathogenic effects may be useful in the clinical treatment of both retinal and neurodegenerative disease.
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