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A genome-wide microRNA profiling indicates miR-424-5p and miR-503-5p as regulators of ALK expression in neuroblastoma(NB Samples)

ABSTRACT: The discovery of either missense mutations or amplification of ALK (Anaplastic Lymphoma Kinase) gene identified this receptor tyrosine kinase as a therapeutic target in neuroblastoma (NB). Moreover, a high ALK expression has been associated with cases of metastatic NB and with a worse prognosis. In order to identify miRNAs involved in the regulation of ALK expression in NB we therefore analyzed their expression profile in 16 NB cell lines and in 22 patients by qPCR. We then identified miRNAs which were differentially expressed between two groups of samples showing high (ALK+) or low (ALK-) expression levels of ALK by using microarrays containing 866 human miRNA probes (Agilent). Next, the differential expression analysis between the two groups (ALK+ and ALK-) was performed using R. Our analysis showed a higher expression of 30 and 23 miRNAs (p-value <0.05) in NB lines and samples, respectively, both belonging to the ALK- group. Validation analysis and filtering according to in silico suggested miR-424-5p as a potential ALK regulator candidate. Dual luciferase assay indicated a direct binding of this miRNA to ALK-3’UTR. Moreover, we observed a down-regulation of ALK protein expression following transfection of miR-424-5p mimic as well as inhibition of cell viability in ALK+ NB cell lines. In conclusion, our data suggest miR-424-5p as involved in the regulation of ALK expression in NB.

ORGANISM(S): Homo sapiens

PROVIDER: GSE86652 | GEO | 2017/04/30

SECONDARY ACCESSION(S): PRJNA342484

REPOSITORIES: GEO

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Project description:Physical exercise stimulates adult hippocampal neurogenesis in mammals, and is considered a relevant strategy for preventing age-related cognitive decline in aging humans. However, its mechanism is controversial. Here, by investigating microRNAs (miRNAs) and their downstream pathways, we uncover that downregulation of miR-135a-5p mediates exercise-induced proliferation of adult NPCs in adult neurogenesis in the mouse hippocampus, likely by activation of phosphatidylinositol (IP3) signaling. Specifically, while overexpression of miR-135 prevents exercise-induced proliferation in the adult mouse hippocampus in vivo and in NPCs in vitro, its inhibition activates NPCs proliferation in resting and aged mice. Label free proteomics and bioinformatics analysis identifies 11 potential targets of miR-135 in NPCs, several of them involved in phosphatidylinositol signaling. Thus, miR-135a is key in mediating exercise-induced adult neurogenesis and opens intriguing perspectives toward the therapeutic exploitation of miR-135 to delay or prevent pathological brain ageing.Physical exercise stimulates adult hippocampal neurogenesis in mammals, and is considered a relevant strategy for preventing age-related cognitive decline in aging humans. However, its mechanism is controversial. Here, by investigating microRNAs (miRNAs) and their downstream pathways, we uncover that downregulation of miR-135a-5p mediates exercise-induced proliferation of adult NPCs in adult neurogenesis in the mouse hippocampus, likely by activation of phosphatidylinositol (IP3) signaling. Specifically, while overexpression of miR-135 prevents exercise-induced proliferation in the adult mouse hippocampus in vivo and in NPCs in vitro, its inhibition activates NPCs proliferation in resting and aged mice. Label free proteomics and bioinformatics analysis identifies 11 potential targets of miR-135 in NPCs, several of them involved in phosphatidylinositol signaling. Thus, miR-135a is key in mediating exercise-induced adult neurogenesis and opens intriguing perspectives toward the therapeutic exploitation of miR-135 to delay or prevent pathological brain ageing.

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A genome-wide microRNA profiling indicates miR-424-5p and miR-503-5p as regulators of ALK expression in neuroblastoma(NB Samples)

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