Department of Neurosurgery, First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, 510080, China.
Department of Neurosurgery, The Six Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China.
Cell Death Dis. 2021 Jan 4;12(1):14. doi: 10.1038/s41419-020-03307-x.
Glioma is one of the most commonly diagnosed intracranial malignant tumors with extremely high morbidity and mortality, whose treatment was seriously limited because of the unclear molecular mechanism. In this study, in order to identify a novel therapeutic target for glioma treatment, we explored the functions and mechanism of MEX3A in regulating glioma. The immunohistochemical staining of MEX3A in glioma and normal tissues revealed the upregulation of MEX3A and further indicated the relationship between high MEX3A expression and higher malignancy as well as poorer prognosis of glioma. In vitro loss-of-function and gain-of-function experiments comprehensively demonstrated that MEX3A may promote glioma development through regulating cell proliferation, cell apoptosis, cell cycle, and cell migration. In vivo experiments also suggested the inhibition of glioma growth by MEX3A knockdown. Moreover, our mechanistic study identifies CCL2 as a potential downstream target of MEX3A, which possesses similar regulatory effects on glioma development with MEX3A and could attenuate the promotion of glioma induced by MEX3A overexpression. Overall, MEX3A was identified as a potential tumor promoter in glioma development and therapeutic target in glioma treatment.
神经胶质瘤是最常见的颅内恶性肿瘤之一,发病率和死亡率极高,由于分子机制不清楚,其治疗受到严重限制。在这项研究中,为了确定治疗神经胶质瘤的新的治疗靶点,我们探讨了 MEX3A 在调节神经胶质瘤中的功能和机制。神经胶质瘤和正常组织中 MEX3A 的免疫组织化学染色显示 MEX3A 的上调,进一步表明高 MEX3A 表达与神经胶质瘤的更高恶性程度和更差预后之间存在关系。体外功能丧失和功能获得实验全面表明,MEX3A 可能通过调节细胞增殖、细胞凋亡、细胞周期和细胞迁移来促进神经胶质瘤的发展。体内实验也表明 MEX3A 敲低抑制神经胶质瘤的生长。此外,我们的机制研究确定 CCL2 是 MEX3A 的一个潜在下游靶标,它对神经胶质瘤的发展具有与 MEX3A 相似的调节作用,并能减弱 MEX3A 过表达诱导的神经胶质瘤的促进作用。总的来说,MEX3A 被确定为神经胶质瘤发展中的潜在肿瘤促进因子和神经胶质瘤治疗中的治疗靶点。