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

Abstract

It has been reported that the miR-106bB25 cluster, a paralog of the miR-17B92 cluster, possesses oncogenic activities. However, the precise role of each microRNA (miRNA) in the miR-106bB25 cluster is not yet known. In this study, we examined the function of miR-93, one of the microRNAs within the miR-106bB25 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 integrinb8 is a target of miR-93. Higher levels of integrin-b8 are associated with cell death in tumor mass and in human glioblastoma. Silencing of integrin-b8 expression using small interfering RNA promoted cell proliferation, whereas ectopic expression of integrin-b8 decreased cell growth. These findings showed that miR-93 promotes tumor growth and angiogenesis by suppressing, at least in part, integrin-b8 expression. Our results suggest that inhibition of miR-93 function may be a feasible approach to suppress angiogenesis and tumor growth.

Expression of MiR200a, miR93, Metastasis-related Gene RECK and MMP2/MMP9 in Human Cervical Carcinoma - Relationship with Prognosis

“…The miR-93 gene is located on chromosome 7q22.1, it can suppress proliferation and differentiation of cancer stem cells, while promoting tumor growth and malignant cells survival (Fang et al, 2011;Yu et al, 2011;Suling et al, 2012). In the present study, mir-93 expression was 5.29 fold higher compared to normal tissue.…”

Systems Analysis of the NCI-60 Cancer Cell Lines by Alignment of Protein Pathway Activation Modules with “-OMIC” Data Fields and Therapeutic Response Signatures

“…Other downregulated putative targets were found to be involved in cytokine interaction and cellular adhesion, strengthening the evidence for involvement of these miRNAs in adhesion, including the integrin pathway (31). miR-17-92 has been shown to inhibit collagen synthesis by targeting TGFbR2, in mice (32), as well as it is known that miR-93 promotes angiogenesis and tumor growth by targeting integrinb8 (33), and together with mir-106a, seems to directly target the Cofilin2 gene (34).…”

The correlation of circulating pro‐angiogenic miRNAs’ expressions with disease risk, clinicopathological features, and survival profiles in gastric cancer

“…Furthermore, increasing studies have demonstrated that several miRNAs take part in the processes of angiogenesis and they play crucial roles in the progress or prognosis of cancers such as hepatocellular carcinoma, human colon cancer, and bladder cancer 20, 21, 22. For example, in a study conducted by Fang et al,23 miR‐93 represses integrin‐β8 expression, thereby allowing spreading of endothelial cells, and consequently promotes angiogenesis in glioma. It is also revealed that miR‐126 facilitates angiogenesis of GC through regulating vascular endothelial growth factor (VEGF) level, which is an important regulator in vasculogenesis 18.…”