MiR-148a impairs Ras/ERK signaling in B lymphocytes by targeting SOS proteins.

MiR-148a impairs Ras/ERK signaling in B lymphocytes by targeting SOS proteins.

Oncotarget. 2017 May 07;:

Authors: Alles J, Ludwig N, Rheinheimer S, Leidinger P, Grässer FA, Keller A, Meese E

Abstract
Although microRNAs have been recognized as central cellular regulators, there is an evident lack of knowledge about their targets. Here, we analyzed potential target genes for miR-148a functioning in Ras signaling in B cells, including SOS1 and SOS2. A dual-luciferase reporter assay showed significantly decreased luciferase activity upon ectopic overexpression of miR-148a in HEK-293T cells that were co-transfected with the 3'UTR of either SOS1 or SOS2. Each of the 3'UTRs of SOS1 and SOS2 contained two binding sites for miR-148a both of which were necessary for the decreased luciferase activity. MiR-148a overexpression in HEK-293T lead to significantly reduced levels of both endogenous SOS1 and SOS2 proteins. Likewise, reduced levels of SOS proteins were found in two B cell lines that were transfected with miR-148a. The level of ERK1/2 phosphorylation as one of the most relevant downstream members of the Ras/ERK signaling pathway was also reduced in cells with miR-148a overexpression. The data show that miR-148a impairs the Ras/ERK signaling pathway via SOS1 and SOS2 proteins in B cells.

PMID: 28525902 [PubMed - as supplied by publisher]

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