mi RNA expression is modulated over time after focal ischaemia: up-regulation of miR-347 promotes neuronal apoptosis.

Autor: Gubern, Carme, Camós, Susanna, Ballesteros, Iván, Rodríguez, Rocío, Romera, Víctor G., Cañadas, Roberto, Lizasoain, Ignacio, Moro, María A., Serena, Joaquín, Mallolas, Judith, Castellanos, Mar
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Zdroj: FEBS Journal; Dec2013, Vol. 280 Issue 23, p6233-6246, 14p
Abstrakt: Despite the large number of molecules reported as being over-expressed after ischaemia, little is known regarding their regulation. mi RNAs are potent post-transcriptional regulators of gene expression, and reports have shown differentially mi RNA expression in response to focal cerebral ischaemia. The present study analysed mi RNA expression from acute to late phases of ischaemia to identify specific ischaemia-related mi RNAs, elucidate their role, and identify potential targets involved in stroke pathophysiology. Of 112 mi RNAs, 32 showed significant changes and different expression profiles. In addition to the previously reported differentially expressed mi RNAs, new ischaemia-regulated mi RNAs have been found, including miR-347. Forty-seven genes involved in brain functions or related to ischaemia are predicted to be potential targets of the differentially expressed mi RNAs after middle cerebral artery occlusion. Analysis of four of these targets (Acsl4, Arf3, Btg2 and Dpysl5) showed them to be differentially regulated by ischaemia at the transcriptional or post-transcriptional level. Acsl4, Bnip3l and Phyhip, potential targets of miR-347, were up-regulated after miR-347 over-expression, inducing neuronal apoptotic death. Our findings suggest that miR-347 plays an important role in regulating neuronal cell death, identify Acsl4 as a new protein requiring study in ischaemia, and provide an important resource for future functional studies of mi RNAs after ischaemia. [ABSTRACT FROM AUTHOR]
Databáze: Complementary Index
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