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MicroRNA miR-93 promotes tumor growth and angiogenesis by targeting integrin-β8
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Journal Article
MicroRNA miR-93 promotes tumor growth and angiogenesis by targeting integrin-β8
2011
Overview
It has been reported that the miR-106b∼25 cluster, a paralog of the miR-17∼92 cluster, possesses oncogenic activities. However, the precise role of each microRNA (miRNA) in the miR-106b∼25 cluster is not yet known. In this study, we examined the function of miR-93, one of the microRNAs within the miR-106b∼25 cluster, in angiogenesis and tumor formation. We found that
miR-93
enhanced cell survival, promoted sphere formation and augmented tumor growth. Most strikingly, when miR-93-overexpressing U87 cells were co-cultured with endothelial cells, they supported endothelial cell spreading, growth, migration and tube formation.
In vivo
studies revealed that
miR-93
-expressing cells induced blood vessel formation, allowing blood vessels to extend to tumor tissues in high densities. Angiogenesis promoted by
miR-93
in return facilitated cell survival, resulting in enhanced tumor growth. We further showed that integrin-β8 is a target of
miR-93
. Higher levels of integrin-β8 are associated with cell death in tumor mass and in human glioblastoma. Silencing of integrin-β8 expression using small interfering RNA promoted cell proliferation, whereas ectopic expression of integrin-β8 decreased cell growth. These findings showed that miR-93 promotes tumor growth and angiogenesis by suppressing, at least in part, integrin-β8 expression. Our results suggest that inhibition of
miR-93
function may be a feasible approach to suppress angiogenesis and tumor growth.
Publisher
Nature Publishing Group UK,Nature Publishing Group
Subject
/ Animals
/ Biological and medical sciences
/ Cell differentiation, maturation, development, hematopoiesis
/ Cell transformation and carcinogenesis. Action of oncogenes and antioncogenes
/ Endothelial Cells - metabolism
/ Fundamental and applied biological sciences. Psychology
/ Growth
/ Humans
/ Integrin beta Chains - metabolism
/ Medicine
/ Mice
/ MicroRNA
/ miRNA
/ Molecular and cellular biology
/ Neovascularization, Pathologic - metabolism
/ Neovascularization, Pathologic - pathology
/ Nervous System Neoplasms - metabolism
/ Nervous System Neoplasms - pathology
/ Oncology
/ RNA, Small Interfering - metabolism
/ siRNA
/ Tumors
