MiR-148a impairs Ras/ERK signaling in B lymphocytes by targeting SOS proteins. Alles, J., Ludwig, N., Rheinheimer, S., Leidinger, P., Grässer, F. A, Keller, A., & Meese, E. Oncotarget, 8:56417–56427, August, 2017.
doi  abstract   bibtex   
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.
@Article{Alles2017,
  author       = {Alles, Julia and Ludwig, Nicole and Rheinheimer, Stefanie and Leidinger, Petra and Grässer, Friedrich A and Keller, Andreas and Meese, Eckart},
  title        = {MiR-148a impairs Ras/ERK signaling in B lymphocytes by targeting SOS proteins.},
  journal      = {Oncotarget},
  year         = {2017},
  volume       = {8},
  pages        = {56417--56427},
  month        = aug,
  issn         = {1949-2553},
  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.},
  completed    = {2017-09-25},
  country      = {United States},
  doi          = {10.18632/oncotarget.17662},
  issn-linking = {1949-2553},
  issue        = {34},
  keywords     = {B cells; ERK; SOS; miR-148a; microRNA},
  nlm-id       = {101532965},
  owner        = {NLM},
  pii          = {17662},
  pmc          = {PMC5593572},
  pmid         = {28915601},
  pubmodel     = {Electronic-eCollection},
  pubstatus    = {epublish},
  revised      = {2017-09-25},
}

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