Neoplasma Vol.69, No.4, p.764–775, 2022
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| Title: miR-520d-3p/MIG-7 axis regulates vasculogenic mimicry formation and metastasis in osteosarcoma |
| Author: Nan Yao, Jing Zhou, Jie Song, Yantao Jiang, Jian Zhang |
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Abstract: Vasculogenic mimicry (VM) refers to a novel mode of tumor microcirculation, which provides an escape route for tumor metastasis, and thereby correlates with a poor prognosis. We previously reported MIG-7 plays a pivotal role in osteosarcoma (OS) VM. However, the precise mechanism of MIG-7 in regulating OS VM remains to be elucidated. The expression levels of miR-520d-3p and MIG-7 were measured in OS cell lines. The effects of the miR-520d-3p/MIG-7 axis were investigated by in vitro functional assays. An orthotopic xenograft model was established to assess the role of the miR-520d-3p/MIG-7 axis in OS cells in vivo. Phalloidin staining, western blot, immunohistochemistry, ELISA assays were carried out to explore the molecular events that were involved in the miR-520d-3p/MIG-7 axis-mediated VM formation. The miR-520d-3p expression level was inversely correlated with MIG-7 in these cell lines. miR-520d-3p overexpression suppressed the proliferation, migration, invasion, VM, and promotes the adhesion of OS cells in vitro. miR-520d-3p could directly bind to the 3'-UTR of MIG-7 and regulated MIG-7 expression, which led to impaired lamellipodia and filopodia formation and inactivation of the PI3K/MMPs/Ln-5γ2 signaling pathway. The anti-metastatic and anti-VM effects of miR-520d-3p were confirmed in vivo. Our findings suggest miR-520d-3p acts as a tumor suppressor by inhibiting VM formation in OS via targeting MIG-7.
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| Keywords: osteosarcoma; vasculogenic mimicry; miR-520d-3p; MIG-7; metastasis |
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Published online: 24-Mar-2022
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| Year: 2022, Volume: 69, Issue: 4 |
Page From: 764, Page To: 755 |
doi:10.4149/neo_2022_211128N1683
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