Transcriptome Analysis of Mesenchymal Stem Cells from Multiple Myeloma Patients Reveals Downregulation of Genes Involved in Cell Cycle Progression, Immune Response, and Bone Metabolism
Autor: | Rodrigo Carlini Fernando, Veruska Lia Fook Alves, Edgar Gil Rizzatti, Hatylas Azevedo, Alex Freire Sandes, David Martins, Gisele W. B. Colleoni, Maria Aparecida Dalboni, Diego R. Mazzotti, Mariana Bleker de Oliveira, Fabricio de Carvalho, Angela Isabel Pereira Eugênio |
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Jazyk: | angličtina |
Rok vydání: | 2019 |
Předmět: |
0301 basic medicine
Adult Male lcsh:Medicine Bone Marrow Cells HLA-DR alpha-Chains Biology Article Bone and Bones Bone remodeling Transcriptome 03 medical and health sciences 0302 clinical medicine Immune system Downregulation and upregulation Gene expression medicine Tumor Microenvironment Humans lcsh:Science Multiple myeloma Aged Aged 80 and over Tumor microenvironment Multidisciplinary Gene Expression Profiling lcsh:R Mesenchymal stem cell Mesenchymal Stem Cells Middle Aged medicine.disease 030104 developmental biology Cancer research lcsh:Q Female Multiple Myeloma 030217 neurology & neurosurgery Cell Division |
Zdroj: | Scientific Reports Scientific Reports, Vol 9, Iss 1, Pp 1-16 (2019) |
ISSN: | 2045-2322 |
Popis: | A growing body of evidence suggests a key role of tumor microenvironment, especially for bone marrow mesenchymal stem cells (MSC), in the maintenance and progression of multiple myeloma (MM), through direct and indirect interactions with tumor plasma cells. Thus, this study aimed to investigate the gene expression and functional alterations of MSC from MM patients (MM-MSC) in comparison with their normal counterparts from normal donors (ND-MSC). Gene expression analysis (Affymetrix) was performed in MM-MSC and ND-MSC after in vitro expansion. To validate these findings, some genes were selected to be evaluated by quantitative real time PCR (RT-qPCR), and also functional in vitro analyses were performed. We demonstrated that MM-MSC have a distinct gene expression profile than ND-MSC, with 485 differentially expressed genes (DEG) - 280 upregulated and 205 downregulated. Bioinformatics analyses revealed that the main enriched functions among downregulated DEG were related to cell cycle progression, immune response activation and bone metabolism. Four genes were validated by qPCR - ZNF521 and SEMA3A, which are involved in bone metabolism, and HLA-DRA and CHIRL1, which are implicated in the activation of immune response. Taken together, our results suggest that MM-MSC have constitutive abnormalities that remain present even in the absence of tumors cells. The alterations found in cell cycle progression, immune system activation, and osteoblastogenesis suggest, respectively, that MM-MSC are permanently dependent of tumor cells, might contribute to immune evasion and play an essential role in bone lesions frequently found in MM patients. |
Databáze: | OpenAIRE |
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