title: miR-181 elevates Akt signaling by co-targeting PHLPP2 and INPP4B phosphatases in luminal breast cancer.
abstract: The PI3K-Akt pathway is one of the most commonly dysregulated cancer-associated signaling pathways. Here we report an oncogenic function for the miR-181 family in luminal breast cancer cells that involves Akt hyperactivation. We show that miR-181a and miR-181d posttranscriptionally suppress the expression of PHLPP2 and INPP4B phosphatases, resulting in elevated growth factor-induced Akt phosphorylation. Ectopic expression of miR-181a and miR-181d promoted S-phase entry and cell proliferation, which was reversed by pharmacological Akt inhibition. Importantly, the expression of miR-181 family members and PHLPP2/INPP2B are inversely correlated in primary human estrogen receptor-positive breast cancers, supporting the clinical relevance of our findings.
authors.affiliation: Institute of Cell Biology and Immunology, University of Stuttgart, 70569, Stuttgart, Germany.
authors.forename: Michaela
authors.initials: M
authors.lastname: Strotbek
authors.affiliation: Institute of Cell Biology and Immunology, University of Stuttgart, 70569, Stuttgart, Germany.
authors.forename: Simone
authors.initials: S
authors.lastname: Schmid
authors.affiliation: Institute of Cell Biology and Immunology, University of Stuttgart, 70569, Stuttgart, Germany.
authors.forename: Ismael
authors.initials: I
authors.lastname: Sánchez-González
authors.affiliation: Institute of Molecular Medicine and Cell Research, Albert-Ludwigs-University Freiburg, 79104, Freiburg, Germany.|German Cancer Consortium (DKTK) and German Cancer Research Center (DKFZ), Heidelberg, 69120, Germany.
authors.forename: Melanie
authors.initials: M
authors.lastname: Boerries
authors.affiliation: Institute of Molecular Medicine and Cell Research, Albert-Ludwigs-University Freiburg, 79104, Freiburg, Germany.|German Cancer Consortium (DKTK) and German Cancer Research Center (DKFZ), Heidelberg, 69120, Germany.|Lübeck Institute of Experimental Dermatology, University of Lübeck, Lübeck, Germany.
authors.forename: Hauke
authors.initials: H
authors.lastname: Busch
authors.affiliation: Institute of Cell Biology and Immunology, University of Stuttgart, 70569, Stuttgart, Germany.|Stuttgart Research Center Systems Biology (SRCSB), University of Stuttgart, Stuttgart, Germany.
authors.forename: Monilola A
authors.identifier: 0000-0003-1093-263X
authors.initials: MA
authors.lastname: Olayioye
mesh_terms: D017209:Apoptosis; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D002453:Cell Cycle; D049109:Cell Proliferation; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D035683:MicroRNAs / Q000235:genetics*; D010749:Phosphoprotein Phosphatases / Q000235:genetics / Q000378:metabolism*; D010744:Phosphoric Monoester Hydrolases / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D014407:Tumor Cells, Cultured
chemical_list: C000608460:MIRN-181 microRNA, human; D035683:MicroRNAs; D012333:RNA, Messenger; D051057:Proto-Oncogene Proteins c-akt; C541572:PHLPP2 protein, human; D010749:Phosphoprotein Phosphatases; D010744:Phosphoric Monoester Hydrolases; C053153:phosphatidylinositol-3,4-bisphosphate 4-phosphatase
keywords: PI3K-Akt pathway; breast cancer; lipid and protein phosphatases; microRNA/miRNA; receptor tyrosine kinase signaling