Department of Neurosurgery, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai, China.
National Center for Neurological Disorders, Beijing, China.
Cell Mol Neurobiol. 2023 Aug;43(6):2975-2987. doi: 10.1007/s10571-023-01348-2. Epub 2023 Apr 20.
Gliomas are aggressive brain tumors characterized by uncontrolled cell proliferation. FAM64A, a cell cycle-related gene, has been found to promote cell proliferation in various tumors, including gliomas. However, the regulatory mechanism and clinical significance of FAM64A in gliomas remain unclear. In this study, we investigated FAM64A expression in gliomas with different grades and constructed FAM64A silenced cell lines to study its functions. Our results demonstrated that FAM64A was highly expressed in glioblastoma (P < 0.001) and associated with a poor prognosis (P < 0.001). Expression profiles at the single-cell resolution indicated FAM64A could play a role in a cell-cycle-dependent way to promote glioma cell proliferation. We further observed that FAM64A silencing in glioma cells resulted in disrupted proliferation and migration ability, and increased cell accumulation in the G2/M phase (P = 0.034). Additionally, TGF-β signaling upregulates FAM64A expression, and SMAD4 and FAM64A co-localize in high-grade glioma tissues. We found FAM64A knockdown inhibited TGF-β-induced epithelial-mesenchymal transition in glioma. Our findings suggest that FAM64A could serve as a diagnostic and therapeutic target in gliomas.
神经胶质瘤是一种具有不受控制的细胞增殖特征的侵袭性脑肿瘤。细胞周期相关基因 FAM64A 已被发现可促进多种肿瘤（包括神经胶质瘤）的细胞增殖。然而，FAM64A 在神经胶质瘤中的调控机制和临床意义仍不清楚。在这项研究中，我们研究了不同分级的神经胶质瘤中 FAM64A 的表达，并构建了 FAM64A 沉默的细胞系以研究其功能。我们的结果表明 FAM64A 在胶质母细胞瘤中高表达（P < 0.001），与不良预后相关（P < 0.001）。单细胞分辨率的表达谱表明 FAM64A 可能以细胞周期依赖性方式发挥作用，促进神经胶质瘤细胞增殖。我们进一步观察到，在神经胶质瘤细胞中沉默 FAM64A 会导致增殖和迁移能力受损，并增加 G2/M 期的细胞积累（P = 0.034）。此外，TGF-β 信号通路上调 FAM64A 的表达，并且 SMAD4 和 FAM64A 在高级别神经胶质瘤组织中共定位。我们发现 FAM64A 敲低抑制了 TGF-β 诱导的神经胶质瘤上皮-间充质转化。我们的研究结果表明 FAM64A 可作为神经胶质瘤的诊断和治疗靶点。
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