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MicroRNA miR-93 promotes tumor growth and angiogenesis by targeting integrin-β8

Oncogene volume 30, pages 806–821 (2011)Cite this article

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Abstract

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.

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Acknowledgements

We thank the Brain Tumour Tissue Bank (London, Ontario) for glioblastoma slides. This work was supported by a grant from the Heart and Stroke Foundation of Ontario (NA6282) and a grant from Canadian Institutes of Health Research (MOP-102635) to BBY, who is the recipient of a Career Investigator Award (CI5958) from the Heart and Stroke Foundation of Ontario. LF is supported by a Scholarship from China Scholarship Council. CP is supported by a Mid-Career Award from Ontario Women's Health Council/CIHR.

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Authors and Affiliations

  1. Sunnybrook Research Institute, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada,

    L Fang, Z Deng, T Shatseva, W W Du, A J Yee, S W Shan & B B Yang

  2. China-Japan Union Hospital of Jilin University, Jilin, China

    L Fang & C He

  3. Department of Biology, York University, Toronto, Ontario, Canada,

    J Yang & C Peng

  4. Department of Pathology, University of Western Ontario, London, Ontario, Canada,

    L C Ang

  5. Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada,

    L Fang, Z Deng, T Shatseva, S W Shan & B B Yang

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  1. L Fang
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Correspondence to B B Yang.

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Fang, L., Deng, Z., Shatseva, T. et al. MicroRNA miR-93 promotes tumor growth and angiogenesis by targeting integrin-β8. Oncogene 30, 806–821 (2011). https://doi.org/10.1038/onc.2010.465

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