miR-375 Regulates Invasion-Related Proteins Vimentin and L-Plastin
| Autor: | Jihyeon Lim, Ruth Hogue Angeletti, Thomas J. Belbin, Nicole Kawachi, Thomas J. Ow, Thomas M. Harris, Jeffrey E. Segall, Michael B. Prystowsky, Berta Burd, Geoffrey Childs, Lizandra Jimenez |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Proteomics Invadopodium Down-Regulation Vimentin Biology Models Biological Pathology and Forensic Medicine 03 medical and health sciences Downregulation and upregulation Mir-375 medicine Humans Neoplasm Invasiveness Transcription factor Regulation of gene expression Gene knockdown Squamous Cell Carcinoma of Head and Neck Microfilament Proteins Regular Article medicine.disease Molecular biology Head and neck squamous-cell carcinoma Neoplasm Proteins Gene Expression Regulation Neoplastic MicroRNAs 030104 developmental biology Head and Neck Neoplasms Gene Knockdown Techniques Core Binding Factor Alpha 2 Subunit biology.protein Carcinoma Squamous Cell |
| Zdroj: | The American journal of pathology. 187(7) |
| ISSN: | 1525-2191 |
| Popis: | Invasion is a hallmark of advanced head and neck squamous cell carcinoma (HNSCC). We previously determined that low relative miR-375 expression was associated with poor patient prognosis. HNSCC cells with increased miR-375 expression have lower invasive properties and impaired invadopodium activity. Using stable isotope labeling with amino acids in cell culture and reverse-phase liquid chromatography mass spectrometry, we assessed the impact of miR-375 expression on protein levels in UM-SCC-1 cells. Increased miR-375 expression was associated with down-regulation of proteins involved in cellular assembly and organization, death and survival, and movement. Two invasion-associated proteins, vimentin and L-plastin, were strongly down-regulated by miR-375. Luciferase reporter assays demonstrated that high miR-375 expression reduced vimentin promoter activity, suggesting that vimentin is an indirect target of miR-375. Runt-related transcription factor 1 (RUNX1) is a potential miR-375 direct target, and its knockdown reduced vimentin and L-plastin expression. Data in The Cancer Genome Atlas HNSCC database showed a significant inverse correlation between miR-375 expression and RUNX1, vimentin, and L-plastin RNA expression. These clinical correlations validate our in vitro model findings and support a mechanism in which miR-375 suppresses RUNX1 levels, resulting in reduced vimentin and L-plastin expression. Furthermore, knockdown of RUNX1, L-plastin, and vimentin resulted in significant reductions in cell invasion in vitro , indicating the functional significance of miR-375 regulation of specific proteins involved in HNSCC invasion. |
| Databáze: | OpenAIRE |
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