Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha, Hunan, China.
Department of Pathology, Changsha Central Hospital, Changsha, Hunan, China.
Biochem Biophys Res Commun. 2021 Apr 9;548:67-73. doi: 10.1016/j.bbrc.2021.02.062. Epub 2021 Feb 23.
The expression and roles of FLOT2, especially for its underlying mechanism, in gliomas have been rarely revealed. In this study, upregulations of both FLOT2 and EphA2 in gliomas tissues were validated by immunohistochemistry (IHC) staining and Western blot. FLOT2 silencing notably inhibited the growth and invasion of gliomas cells. Simultaneously, FLOT2 depletion suppressed Akt and NF-κB activities, induced apoptosis, cell cycle arrest, and epithelial-mesenchymal transition (EMT) inhibition, demonstrated by expression alterations of key proteins of the above processes. Mechanistically, FLOT2 could maintain EphA2 stability viainteraction, and restoration of EphA2 could remarkably release the suppressive effects on gliomas cells induced by FLOT2 knockdown. Lastly, FLOT2 and EphA2, whose protein and mRNA levels are both positively correlated in gliomas, shows significant association with clinical characteristics like Ki67 intensity, p53 expression, and tumor stage in patients with gliomas. In conclusion, our results reveal the upregulation, oncogenic roles of FLOT2, and the corresponding underlying mechanism in gliomas, highlighting that the FLOT2-EphA2 axis is served as a promising therapeutic target for gliomas.
FLOT2 的表达和作用，特别是其潜在机制，在神经胶质瘤中很少被揭示。在这项研究中，通过免疫组织化学（IHC）染色和 Western blot 验证了 FLOT2 和 EphA2 在神经胶质瘤组织中的上调。FLOT2 沉默显著抑制了神经胶质瘤细胞的生长和侵袭。同时，FLOT2 耗竭抑制了 Akt 和 NF-κB 的活性，诱导了细胞凋亡、细胞周期停滞和上皮-间充质转化（EMT）抑制，这通过上述过程关键蛋白的表达变化来证明。在机制上，FLOT2 可以通过相互作用维持 EphA2 的稳定性，并且 EphA2 的恢复可以显著释放由 FLOT2 敲低引起的对神经胶质瘤细胞的抑制作用。最后，FLOT2 和 EphA2 在神经胶质瘤中的蛋白和 mRNA 水平均呈正相关，与神经胶质瘤患者的 Ki67 强度、p53 表达和肿瘤分期等临床特征显著相关。总之，我们的结果揭示了 FLOT2 在神经胶质瘤中的上调和致癌作用及其相应的潜在机制，突出了 FLOT2-EphA2 轴作为神经胶质瘤有前途的治疗靶点。
