miR-15a and miR-16 affect the angiogenesis of multiple myeloma by targeting VEGF
| Autor: | Lisha Ai, Xiao-Mei She, You Qin, Lu Zhang, Chunyan Sun, Yu Hu, Zhang-Bo Chu, Lei Chen |
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| Rok vydání: | 2012 |
| Předmět: |
Male
Vascular Endothelial Growth Factor A Cancer Research Angiogenesis Blotting Western Plasma Cells Mice Nude Apoptosis Mice SCID Biology Real-Time Polymerase Chain Reaction medicine.disease_cause Monoclonal Gammopathy of Undetermined Significance Immunoenzyme Techniques Neovascularization Mice chemistry.chemical_compound Cell Movement Mice Inbred NOD microRNA Cell Adhesion medicine Animals Humans RNA Messenger 3' Untranslated Regions Cell Proliferation Neoplasm Staging Mice Inbred BALB C Neovascularization Pathologic Oncogene Reverse Transcriptase Polymerase Chain Reaction Cell growth General Medicine Molecular biology Gene Expression Regulation Neoplastic Vascular endothelial growth factor MicroRNAs Vascular endothelial growth factor A chemistry Case-Control Studies Cancer research Female medicine.symptom Multiple Myeloma Carcinogenesis |
| Zdroj: | Carcinogenesis. 34:426-435 |
| ISSN: | 1460-2180 0143-3334 |
| DOI: | 10.1093/carcin/bgs333 |
| Popis: | Deregulated microRNAs (miRNAs) and their roles in cancer development have attracted much attention. Two miRNAs, miR-15a and miR-16, which act as putative tumor suppressor by targeting the oncogene BCL2, have been implicated in cell cycle, apoptosis and proliferation. In this study, we investigated the possible role of miR-15a/16 in the angiogenesis of multiple myeloma (MM). Using a stem-loop quantitative reverse transcription-PCR, we analyzed miR-15a/16 expressions in bone marrow samples from newly diagnosed MM patients and a panel of MM cell lines. miRNA transfection, western blotting analysis and assay of luciferase activity were used to examine whether vascular endothelial growth factor (VEGF) is the target of miR-15a/16. The functional roles of miR-15a/16 on tumorigenesis and angiogenesis were examined by in vitro angiogenesis models and in vivo tumor xenograft model. We showed that miR-15a and miR-16 were significantly underexpressed in primary MM cells as well as in MM cell lines. The aberrant expression of miR-15a/16 was detected especially in advanced stage MM. In human MM cell lines and normal plasma cells, expression of miR-15a/16 inversely correlated with the expression of VEGF-A. Western blotting combined with the luciferase reporter assay demonstrated that VEGF-A was a direct target of miR-15a/16. Ectopic overexpression of miR-15a/16 led to decreased pro-angiogenic activity of MM cells. Finally, infection of lentivirus-miR-15a or lentivirus-miR-16 resulted in significant inhibition of tumor growth and angiogenesis in nude mice. This study suggest that miR-15a/16 could play a role in the tumorigenesis of MM at least in part by modulation of angiogenesis through targeting VEGF-A. |
| Databáze: | OpenAIRE |
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