CAMKK2 通过启动子甲基化调控，是弥漫性神经胶质瘤的预后标志物。
CAMKK2, Regulated by Promoter Methylation, is a Prognostic Marker in Diffuse Gliomas.
机构信息
Department of Neurosurgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, Heilong Jiang, China.
出版信息
CNS Neurosci Ther. 2016 Jun;22(6):518-24. doi: 10.1111/cns.12531. Epub 2016 Mar 25.
Abstract
AIMS
To explore the expression, methylation pattern, the prognostic value, and the biological consequences of CAMKK2 in gliomas.
METHODS
The expression and methylation pattern of CAMKK2 was inferred and validated from mRNA expression profile (N = 866) and methylation profile (N = 426) of glioma tissue samples, and independent samples were used for further validation by IHC and pyrosequencing. To explore the function of CAMKK2 in gliomas, in vitro studies, colony formation assays and migration and invasion assays were performed.
RESULTS
We found the upregulation of CAMKK2 in high-grade glioma samples was associated with promoter hypomethylation. An elevated expression of CAMKK2 was associated with worse prognosis. By in vitro assays, we demonstrated that CAMKK2 could promote cell migration, invasion, and proliferation.
CONCLUSIONS
The expression level of CAMKK2 could be regulated by promoter methylation. CAMKK2 serves as a prognostic marker in gliomas and could be a potential therapeutic target in gliomas.
摘要
目的
探讨钙调蛋白依赖性蛋白激酶激酶 2（CAMKK2）在脑胶质瘤中的表达、甲基化模式、预后价值及生物学后果。
方法
从脑胶质瘤组织样本的 mRNA 表达谱（N=866）和甲基化谱（N=426）中推断和验证 CAMKK2 的表达和甲基化模式，并通过免疫组织化学和焦磷酸测序对独立样本进行进一步验证。为了探讨 CAMKK2 在脑胶质瘤中的功能，进行了体外研究、集落形成实验、迁移和侵袭实验。
结果
我们发现，CAMKK2 在高级别脑胶质瘤样本中的上调与启动子低甲基化有关。CAMKK2 的高表达与预后不良相关。通过体外实验，我们证明了 CAMKK2 可以促进细胞迁移、侵袭和增殖。
结论
CAMKK2 的表达水平可以通过启动子甲基化来调节。CAMKK2 可作为脑胶质瘤的预后标志物，可能成为脑胶质瘤的潜在治疗靶点。
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