Abstract
BackgroundWnt-5a is a member of the WNT family of secreted lipoglycoproteins, whose expression increases during development; moreover, Wnt-5a plays a key role in synaptic structure and function in the adult nervous system. However, the mechanism underlying these effects is still elusive. MicroRNAs (miRNAs) are a family of small non-coding RNAs that control the gene expression of their targets through hybridization with complementary sequences in the 3′ UTR, thereby inhibiting the translation of the target proteins. Several evidences indicate that the miRNAs are actively involved in the regulation of neuronal function.ResultsIn the present study, we examined whether Wnt-5a modulates the levels of miRNAs in hippocampal neurons. Using PCR arrays, we identified a set of miRNAs that respond to Wnt-5a treatment. One of the most affected miRNAs was miR-101b, which targets cyclooxygenase-2 (COX2), an inducible enzyme that converts arachidonic acid to prostanoids, and has been involved in the injury/inflammatory response, and more recently in neuronal plasticity. Consistent with the Wnt-5a regulation of miR-101b, this Wnt ligand regulates COX2 expression in a time-dependent manner in cultured hippocampal neurons.ConclusionThe biological processes induced by Wnt-5a in hippocampal neurons, involve the regulation of several miRNAs including miR-101b, which has the capacity to regulate several targets, including COX-2 in the central nervous system.
Highlights
Wnt-5a is a member of the WNT family of secreted lipoglycoproteins, whose expression increases during development; Wnt-5a plays a key role in synaptic structure and function in the adult nervous system
We provided evidence for a new mechanism underlying the neuronal effects of Wnt-5a, describing a number of miRNAs responsive to this ligand in hippocampal neurons
We focused on miR-101b, the most affected miRNA through Wnt-5a signaling, and their target COX2, an inducible enzyme that converts arachidonic acid to prostanoids, and has been related to the injury/inflammatory response [31, 32], and more recently to neuronal plasticity [33,34,35,36]
Summary
Wnt-5a is a member of the WNT family of secreted lipoglycoproteins, whose expression increases during development; Wnt-5a plays a key role in synaptic structure and function in the adult nervous system. MicroRNAs (miRNAs) are a family of small non-coding RNAs that control the gene expression of their targets through hybridization with complementary sequences in the 3′ UTR, thereby inhibiting the translation of the target proteins. The genome of mice and humans, has 19 independent genes which are expressed in a tissue-specific form and dependent on the development [1]. On the basis of early studies, these pathways have been classified as either canonical (β-catenin-dependent) or non-canonical (β-catenin-independent) signaling pathways. This classification can only serve as a rough guide, as various divergent pathways has been described in different cellular contexts [9]
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