Background

Glioma is a common malignant tumor of the central nervous system with a high incidence and mortality. Family with sequence similarity 60 member A (FAM60A) is a new subunit of the Sin3 deacetylase complex. The clinical significance and biologic role of FAM60A in glioma remain unclear.

Methods

The expression of FAM60A in normal glial cells, glioma cells, and five-paired gliomas, and adjacent noncancerous tissues was quantified using real-time polymerase chain reaction (PCR) and western blotting. FAM60A protein expression in 179 archived, paraffin-embedded glioma samples was analyzed using immunohistochemistry. The roles of FAM60A in glioma cell proliferation and tumorigenicity were explored in vitro and in vivo. The underlying molecular mechanisms were elucidated using Western blot assay. Serum exosomal FAM60A levels of glioma patients were detected using electron microscopy, western blot, and real-time PCR.

Results

FAM60A expression was significantly up-regulated in glioma tissues and cell lines and positively associated with a worse outcome in glioma. Knockdown of FAM60A could inhibit glioma cell proliferation and tumorigenicity in vitro and in vivo. Besides, FAM60A expression was detectable in extracted serum exosomes with a higher expression in the glioma cancer group than in the normal group.

Conclusions

Loss of FAM60A attenuates cell proliferation in glioma by suppressing PI3K/Akt/mTOR signaling pathways. Therefore, FAM60A may act as a prognostic biomarker and therapeutic target for glioma.

中文翻译：

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FAM60A 的缺失通过抑制 PI3K/Akt/mTOR 信号通路减弱胶质瘤中的细胞增殖

背景

胶质瘤是一种常见的中枢神经系统恶性肿瘤，发病率和死亡率都很高。具有序列相似性的家族 60 成员 A (FAM60A) 是 Sin3 脱乙酰酶复合物的新亚基。FAM60A 在胶质瘤中的临床意义和生物学作用仍不清楚。

方法

使用实时聚合酶链反应 (PCR) 和蛋白质印迹法定量 FAM60A 在正常神经胶质细胞、神经胶质瘤细胞和五对神经胶质瘤以及邻近的非癌组织中的表达。使用免疫组织化学分析了 179 个存档的石蜡包埋的神经胶质瘤样本中的 FAM60A 蛋白表达。FAM60A 在神经胶质瘤细胞增殖和致瘤性中的作用在体外和体内进行了探索。使用蛋白质印迹分析阐明了潜在的分子机制。使用电子显微镜、蛋白质印迹和实时 PCR 检测胶质瘤患者的血清外泌体 FAM60A 水平。

结果

FAM60A 表达在神经胶质瘤组织和细胞系中显着上调，并且与神经胶质瘤的较差结果呈正相关。FAM60A 的敲低可以在体外和体内抑制胶质瘤细胞增殖和致瘤性。此外，在提取的血清外泌体中可检测到 FAM60A 表达，胶质瘤癌症组的表达高于正常组。

结论

FAM60A 的缺失通过抑制 PI3K/Akt/mTOR 信号通路减弱神经胶质瘤中的细胞增殖。因此，FAM60A 可以作为神经胶质瘤的预后生物标志物和治疗靶点。