Department of Neurosurgery, Tianjin Medical University General Hospital, Tianjin, China.
Department of Neurosurgery, Tianjin Medical University General Hospital Airport Site, Tianjin, China.
Cell Cycle. 2021 Jul;20(13):1270-1278. doi: 10.1080/15384101.2021.1933303. Epub 2021 May 28.
The metastasis of tumor cells is a challenge for the clinical treatment of glioma. Epithelial-mesenchymal transition (EMT) contributes to glioma cell invasiveness. Our previous study confirmed that the expression of miRNA-451, which inhibits the PI3K/Akt signaling pathway by directly targeting CAB39 and plays a repressive role in glioma, is downregulated in glioma. However, the specific mechanism of miRNA-451 regulation in glioma is unclear. In this study, we investigated whether miRNA-451 blocks the processes of EMT and metastasis in glioma cells in vivo and in vitro. By targeting CAB39, miRNA-451 likely triggers the PI3K/Akt/Snail signaling pathway to reduce glioma proliferation, invasion, migration and EMT. We used Western blotting experiments to demonstrate that overexpression of miRNA-451 significantly reduced p-AKT(Ser473), N-cadherin, Vimentin, Twist, Snail and Cyclin D1 expression and increased E-cadherin expression. We demonstrated that overexpression of miR-451 suppressed glioma cell proliferation, invasion, migration and EMT by MTT and colony formation assays, Transwell assays, wound healing assays and animal experiments. Taken together, these results suggest that miRNA-451 can reduce EMT and metastasis in glioma cells through the suppression of the PI3K/Akt/Snail signaling pathway by targeting CAB39 in vitro and in vivo. miR-451 may be a new target for glioma treatment.
肿瘤细胞的转移是胶质瘤临床治疗的一个挑战。上皮-间质转化（EMT）有助于胶质瘤细胞的侵袭。我们之前的研究证实，miRNA-451 的表达下调与胶质瘤有关，它通过直接靶向 CAB39 抑制 PI3K/Akt 信号通路，对胶质瘤起抑制作用。然而，miRNA-451 在胶质瘤中的具体调控机制尚不清楚。在本研究中，我们研究了 miRNA-451 是否能在体内和体外阻断胶质瘤细胞的 EMT 和转移过程。通过靶向 CAB39，miRNA-451 可能触发 PI3K/Akt/Snail 信号通路，从而减少胶质瘤的增殖、侵袭、迁移和 EMT。我们使用 Western blot 实验证明，miRNA-451 的过表达显著降低了 p-AKT(Ser473)、N-钙黏蛋白、波形蛋白、Twist、Snail 和细胞周期蛋白 D1 的表达，增加了 E-钙黏蛋白的表达。我们通过 MTT 和集落形成实验、Transwell 实验、划痕愈合实验和动物实验证明，miR-451 的过表达通过抑制 PI3K/Akt/Snail 信号通路抑制了胶质瘤细胞的增殖、侵袭、迁移和 EMT。综上所述，这些结果表明，miRNA-451 可通过靶向 CAB39 在体内和体外减少 EMT 和胶质瘤细胞的转移，可能成为治疗胶质瘤的新靶点。
