Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, Jiangsu, China.
Laboratory of Translational Medicine, Jiangsu Province Academy of Traditional Chinese Medicine, Nanjing, Jiangsu, China.
Neoplasma. 2022 Jul;69(4):764-775. doi: 10.4149/neo_2022_211128N1683. Epub 2022 Mar 24.
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.
血管生成拟态（VM）是一种新的肿瘤微循环模式，为肿瘤转移提供了逃逸途径，与预后不良相关。我们之前报道 MIG-7 在骨肉瘤（OS）VM 中发挥关键作用。然而，MIG-7 调节 OS VM 的精确机制仍有待阐明。在 OS 细胞系中测量了 miR-520d-3p 和 MIG-7 的表达水平。通过体外功能测定研究了 miR-520d-3p/MIG-7 轴的作用。建立了原位异种移植模型，以评估 miR-520d-3p/MIG-7 轴在体内 OS 细胞中的作用。进行了鬼笔环肽染色、western blot、免疫组织化学、ELISA 测定，以探讨涉及 miR-520d-3p/MIG-7 轴介导的 VM 形成的分子事件。miR-520d-3p 的表达水平与这些细胞系中的 MIG-7 呈负相关。miR-520d-3p 过表达抑制 OS 细胞的增殖、迁移、侵袭、VM，并促进其体外黏附。miR-520d-3p 可以直接与 MIG-7 的 3'-UTR 结合并调节 MIG-7 的表达，导致片状伪足和丝状伪足形成受损以及 PI3K/MMPs/Ln-5γ2 信号通路失活。miR-520d-3p 在体内的抗转移和抗 VM 作用得到了证实。我们的研究结果表明，miR-520d-3p 通过靶向 MIG-7 抑制 OS 中的 VM 形成发挥肿瘤抑制作用。
