title: Argonaute Family Protein Expression in Normal Tissue and Cancer Entities.
abstract: The members of the Argonaute (AGO) protein family are key players in miRNA-guided gene silencing. They enable the interaction between small RNAs and their respective target mRNA(s) and support the catalytic destruction of the gene transcript or recruit additional proteins for downstream gene silencing. The human AGO family consists of four AGO proteins (AGO1-AGO4), but only AGO2 harbors nuclease activity. In this study, we characterized the expression of the four AGO proteins in cancer cell lines and normal tissues with a new mass spectrometry approach called AGO-APP (AGO Affinity Purification by Peptides). In all analyzed normal tissues, AGO1 and AGO2 were most prominent, but marked tissue-specific differences were identified. Furthermore, considerable changes during development were observed by comparing fetal and adult tissues. We also identified decreased overall AGO expression in melanoma derived cell lines compared to other tumor cell lines and normal tissues, with the largest differences in AGO2 expression. The experiments described in this study suggest that reduced amounts of AGO proteins, as key players in miRNA processing, have impact on several cellular processes. Deregulated miRNA expression has been attributed to chromosomal aberrations, promoter regulation and it is known to have a major impact on tumor development and progression. Our findings will further increase our basic understanding of the molecular basis of miRNA processing and its relevance for disease.
authors: Institute of Biochemistry, Emil-Fischer-Zentrum, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany.
authors: Daniel
authors: D
authors: Völler
authors: Institute of Biochemistry, Emil-Fischer-Zentrum, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany.
authors: Lisa
authors: L
authors: Linck
authors: Biochemistry Center Regensburg, University of Regensburg, Regensburg, Germany.
authors: Astrid
authors: A
authors: Bruckmann
authors: Biochemistry Center Regensburg, University of Regensburg, Regensburg, Germany.
authors: Judith
authors: J
authors: Hauptmann
authors: Biochemistry Center Regensburg, University of Regensburg, Regensburg, Germany.
authors: Rainer
authors: R
authors: Deutzmann
authors: Biochemistry Center Regensburg, University of Regensburg, Regensburg, Germany.
authors: Gunter
authors: G
authors: Meister
authors: Institute of Biochemistry, Emil-Fischer-Zentrum, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany.
authors: Anja Katrin
authors: AK
authors: Bosserhoff
mesh_terms: D060565:Argonaute Proteins / Q000235:genetics / Q000378:metabolism*; D015153:Blotting, Western; D002478:Cells, Cultured; D005333:Fetus / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental; D006801:Humans; D008545:Melanoma / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012867:Skin / Q000378:metabolism*; D012878:Skin Neoplasms / Q000235:genetics / Q000378:metabolism*; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
chemical_list: D060565:Argonaute Proteins; D012333:RNA, Messenger