Argonaute 2 promotes myeloma angiogenesis via microRNA dysregulation
Open Access
- 7 May 2014
- journal article
- research article
- Published by Springer Science and Business Media LLC in Journal of Hematology & Oncology
- Vol. 7 (1), 40
- https://doi.org/10.1186/1756-8722-7-40
Abstract
Dysregulated microRNA (miRNA) expression contributes to cancer cell proliferation, apoptosis and angiogenesis. Angiogenesis is a hallmark of multiple myeloma (MM) development and progression. Argonaute 2 (AGO2) protein, a core component of the RNA-induced silencing complex (RISC), can directly bind to miRNAs and mediate target messenger RNA (mRNA) degradation. A previous study showed that AGO2 knockdown suppressed human umbilical vein endothelial cell (HUVEC) growth and tube formation. However, the roles and molecular mechanisms of AGO2-induced myeloma angiogenesis are not yet fully understood. The aim of this study was to characterize these roles and effects and their associated mechanisms. Supernatants from AGO2-overexpressing MM lines induced HUVEC migration and accelerated tube formation. Conversely, supernatants from AGO2-knockdown MM lines suppressed HUVEC cell migration and tube formation. Moreover, a chick chorioallantoic membrane (CAM) assay was used to demonstrate that AGO2 could drive neovessel formation in MM lines in vivo. Using an miRNA microarray, we observed that 25 miRNAs were upregulated and 7 were downregulated in response to AGO2. Most let-7 family members and 2 miR-17/92 cluster members (miR-17a and miR-92-1), all known pro-angiogenic miRNAs, were positively regulated by AGO2 whereas anti-angiogenic miRNAs such as miR-145 and miR-361 were negatively regulated by AGO2. We conclude that AGO2 can drive neovessel formation in vitro and in vivo by dysregulating the expression of some angiogenic miRNAs. The pro-angiogenic miRNAs of the let-7 family and the miR-17/92 cluster, along with the anti-angiogenic miRNA miR-145, play crucial roles in AGO2-mediated angiogenesis by targeting angiogenesis-related genes.Keywords
This publication has 49 references indexed in Scilit:
- Stilbene derivatives promote Ago2-dependent tumour-suppressive microRNA activityScientific Reports, 2012
- Members of the microRNA-17-92 cluster exhibit a cell-intrinsic antiangiogenic function in endothelial cellsPublished by American Society of Hematology ,2010
- High-risk myeloma is associated with global elevation of miRNAs and overexpression of EIF2C2/AGO2Proceedings of the National Academy of Sciences of the United States of America, 2010
- MicroRNA-145 Suppresses Cell Invasion and Metastasis by Directly Targeting Mucin 1Cancer Research, 2010
- CXC Chemokines in Cancer Angiogenesis and MetastasesAdvances in Cancer Research, 2010
- Dicer-dependent endothelial microRNAs are necessary for postnatal angiogenesisProceedings of the National Academy of Sciences of the United States of America, 2008
- MicroRNAs regulate critical genes associated with multiple myeloma pathogenesisProceedings of the National Academy of Sciences, 2008
- Impaired microRNA processing causes corpus luteum insufficiency and infertility in miceJCI Insight, 2008
- Augmentation of tumor angiogenesis by a Myc-activated microRNA clusterNature Genetics, 2006
- MicroRNA Gene Expression Deregulation in Human Breast CancerCancer Research, 2005