Yang Zhigang, Xu Tao, Xie Tao, Yang Liangliang, Wang Guiping, Gao Yang, Xi Gangming, Zhang Xiaobiao
Department of Neurosurgery, Zhongshan Hospital, Fudan University, Shanghai, China.
Department of Neurosurgery, Changzheng Hospital, Naval Medical University, Shanghai, China.
Cell Death Dis. 2022 Apr 1;13(4):290. doi: 10.1038/s41419-022-04733-9.
Gliomas are the most common brain malignancies characterized by high degree of aggressiveness and high mortality. However, the underlying mechanism of glioma progression remains unclear. Here, we probed the role of CDC42EP3 (CDC42 effector protein 3) played in glioma development and its potential downstream mechanism. The expression of CDC42EP3 in tumor and normal brain tissues were examined through immunohistochemistry and we found the likelihood of CDC42EP3 overexpression was positively correlated with pathological grading. Patients with higher expression of CDC42EP3 were more likely to suffer from recurrence as well. Through constructing CDC42EP3-knockdown cell models, we discovered that silencing CDC42EP3 significantly restricted cell proliferation and migration but facilitated cell apoptosis in vitro. Inhibition on tumor growth mediated by CDC42EP3 depletion was further verified in vivo. Regarding downstream target of CDC42EP3, we found that it may positively regulate the expression of CCND1 through c-Myc-mediated transcription. Furthermore, our findings affirmed that effects of CDC42EP3 overexpression on cell proliferation, migration and apoptosis could be confined by depleting CCND1. In a word, this study reported the tumor-promoting role of CDC42EP3 in glioma progression which probably functioned through targeting CCND1.
神经胶质瘤是最常见的脑恶性肿瘤,具有高度侵袭性和高死亡率。然而,神经胶质瘤进展的潜在机制仍不清楚。在此,我们探究了CDC42EP3(CDC42效应蛋白3)在神经胶质瘤发展中所起的作用及其潜在的下游机制。通过免疫组织化学检测了CDC42EP3在肿瘤组织和正常脑组织中的表达,我们发现CDC42EP3过表达的可能性与病理分级呈正相关。CDC42EP3表达较高的患者也更易复发。通过构建CDC42EP3敲低细胞模型,我们发现在体外沉默CDC42EP3可显著抑制细胞增殖和迁移,但促进细胞凋亡。在体内进一步验证了CDC42EP3缺失介导的对肿瘤生长的抑制作用。关于CDC42EP3的下游靶点,我们发现它可能通过c-Myc介导的转录正向调节CCND1的表达。此外,我们的研究结果证实,通过消耗CCND1可限制CDC42EP3过表达对细胞增殖、迁移和凋亡的影响。总之,本研究报道了CDC42EP3在神经胶质瘤进展中的促肿瘤作用,其可能通过靶向CCND1发挥作用。
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