Department of Neurosurgery, Beijing Chaoyang Integrative Medicine Emergency Medical Center, Beijing, China, 2Department of Cardiology, Characteristic Medical Centre of PAP, He Dong District, Tianjin, China.
Folia Neuropathol. 2021;59(4):359-371. doi: 10.5114/fn.2021.112571.
Gliomas are the most seen tumours in adults in the central nervous system, and high grade of gliomas cause the worse prognose of patients with a shorter survival period. Ubiquitin-specific protease 38 (USP38) has been regarded as the negative regulator of type I interferon signalling; it regulates the ubiquitination process of TANK binding kinase 1 (TBK1). Further study revealed that USP38 also stabilizes the protein lysine-specific histone demethylase 1A (LSD1) via cleaving the ubiquitin chain. However, the effect of USP38 in colorectal cancer was not fully understood.
USP38 overexpression and knockdown vector were constructed using the molecular clone method. The viability rate of U-87MG and U-138MG cells were detected using the Cell Counting Kit-8 (CCK-8) method.The expression and secretion of metastasis-related molecules were detected using the qPCR and ELISA method. The expression of metastasis-related molecules and JAK2/STAT3 signalling pathway was detected using western blotting analysis.
In this study, we firstly constructed a USP38 overexpression and inhibition model in 2 cell lines and found that overexpression of USP38 inhibits the viability rate and migration ability of glioma cells. We further noticed that elevated expression of USP38 reduced the expression and secretion of cell adhesion-related molecules with the elevation in expression of pro-apoptotic proteins, and these effects might be mediated by inhibition of JAK2/STAT3 signalling pathway as USP38 is the upstream regulator of STAT3 and inhibition of cellular adhesion process.
USP38 might be a new therapeutic target for glioma.
神经胶质瘤是成人中枢神经系统最常见的肿瘤，高级别神经胶质瘤导致患者预后较差，生存期较短。泛素特异性蛋白酶 38（USP38）被认为是 I 型干扰素信号的负调节剂；它调节 TANK 结合激酶 1（TBK1）的泛素化过程。进一步的研究表明，USP38 还通过切割泛素链来稳定蛋白赖氨酸特异性组蛋白去甲基化酶 1A（LSD1）。然而，USP38 在结直肠癌中的作用尚未完全了解。
采用分子克隆法构建 USP38 过表达和敲低载体。用细胞计数试剂盒-8（CCK-8）法检测 U-87MG 和 U-138MG 细胞的存活率。用 qPCR 和 ELISA 法检测转移相关分子的表达和分泌。用 Western blot 分析检测转移相关分子和 JAK2/STAT3 信号通路的表达。
在本研究中，我们首先在 2 种细胞系中构建了 USP38 过表达和抑制模型，发现过表达 USP38 抑制神经胶质瘤细胞的活力和迁移能力。我们进一步注意到，USP38 的表达升高降低了细胞黏附相关分子的表达和分泌，同时伴随着促凋亡蛋白表达的升高，这些作用可能是通过抑制 JAK2/STAT3 信号通路介导的，因为 USP38 是 STAT3 的上游调节剂，并抑制细胞黏附过程。
USP38 可能是神经胶质瘤的一个新的治疗靶点。
