Department of Neurosurgery, Central People's Hospital of Zhanjiang, No.236 Yuanzhu Road, Chikan District, Zhanjiang City, Guangdong Province, 524045, People's Republic of China.
Deparment of Neurosurgery, the Affiliated Cancer Hospital & Institute of Guangzhou Medical University, Guangzhou City, Guangdong Province, 510080, People's Republic of China.
Metab Brain Dis. 2022 Apr;37(4):1133-1143. doi: 10.1007/s11011-022-00925-6. Epub 2022 Mar 7.
Glioblastoma (GBM), a predominant central nervous system (CNS) malignancy, is correlated with high mortality and severe morbidity. Mammalian methyltransferase-like 7B (METTL7B) as a methyltransferase has been identified to participate in cancer progression. However, its function in GBM is elusive. Accordingly, we aimed to explore the effect of METTL7B on GBM. The expression of METTL7B and EGR2 in GBM patients and GBM cells were detected by qPCR, western blots and immunohistochemical staining. Cell viability was assessed by CCK-8 assays. Cell proliferation was determined by EdU, colony formation, and tumor sphere formation assays. METTL7B shRNA was injected into the Balb/c nude mice. The size and weight of isolated tumor was measured. And the expression levels of Ki67, METTL7B and EGR1 were examined by immunohistochemical staining. METTL7B was significantly elevated, while EGR1 was downregulated in clinical GBM tissues. METTL7B upregulation was associated with the low overall survival of GBM patients. Moreover, METTL7B depletion remarkably attenuated GBM cell proliferation. Mechanistically, METTL7B overexpression inhibited EGR1 expression in GBM cells. EGR1 knockdown rescued the inhibitory effect of METTL7B depletion on GBM cell proliferation. Meanwhile, METTL7B depletion arrested more GBM cells at the G0/G1, but fewer cells at the S phase, which EGR1 knockdown reversed these effects. Furthermore, tumorigenicity analysis revealed that METTL7B promotes tumor growth of GBM cells in vivo. METTL7B contributes to the malignant progression of GBM by inhibiting EGR1 expression. METTL7B and EGR1 may be utilized as the treatment targets for GBM therapy.
胶质母细胞瘤（GBM）是一种主要的中枢神经系统（CNS）恶性肿瘤，与高死亡率和严重发病率相关。哺乳动物甲基转移酶样 7B（METTL7B）作为一种甲基转移酶，已被确定参与癌症进展。然而，其在 GBM 中的功能尚不清楚。因此，我们旨在探讨 METTL7B 对 GBM 的影响。通过 qPCR、western blot 和免疫组织化学染色检测 GBM 患者和 GBM 细胞中 METTL7B 和 EGR2 的表达。通过 CCK-8 测定评估细胞活力。通过 EdU、集落形成和肿瘤球形成测定确定细胞增殖。将 METTL7B shRNA 注入 Balb/c 裸鼠。测量分离肿瘤的大小和重量。并通过免疫组织化学染色检测 Ki67、METTL7B 和 EGR1 的表达水平。METTL7B 在临床 GBM 组织中显著上调，而 EGR1 下调。METTL7B 上调与 GBM 患者的总生存率降低相关。此外，METTL7B 耗竭显著抑制 GBM 细胞增殖。机制上，METTL7B 过表达抑制 GBM 细胞中 EGR1 的表达。EGR1 敲低挽救了 METTL7B 耗竭对 GBM 细胞增殖的抑制作用。同时，METTL7B 耗竭使更多的 GBM 细胞停滞在 G0/G1 期，但 S 期的细胞更少，而 EGR1 敲低逆转了这些效应。此外，肿瘤发生分析表明，METTL7B 在体内促进 GBM 细胞的肿瘤生长。METTL7B 通过抑制 EGR1 表达促进 GBM 的恶性进展。METTL7B 和 EGR1 可作为 GBM 治疗的治疗靶点。
