关键词:

肿瘤坏死因子α诱导蛋白3相互作用蛋白1,  , 核因子κB,  , TNF受体相关因子6,  , 胶质瘤

Abstract:

Objective To explore the mechanism of TNFα ⁃ induced protein 3 ⁃ interacting protein1 （TNIP1）in the regulation of nuclear factor kappa B （NF ⁃ κB）signaling pathway in IDH wild ⁃type glioma. Methods The CGGA and TCGA databases were used to determine the expression and prognostic value of TNIP1 in IDH wild⁃type gliomas. The expression of TNIP1 in N33 cells was knocked down with specific siRNA，and the cell proliferation and migration ability were analyzed by CCK⁃8 test，Transwell migration test，and scratch test. The interaction between TNIP1 and TNF receptor ⁃ related factor 6（TRAF6）and its influence on the ubiquitination of TRAF6 were analyzed by immunoprecipitation. U87 cells expressing an empty vector，oe⁃TNIP1 or si⁃TNIP1 were injected into the brain of nude mice，and the tumor growth was monitored by BLI method. Results TNIP1 expres⁃ sion was positively associated with a higher malignant grade and poorer prognosis of IDH⁃wild type gliomas but not IDH ⁃ mutant gliomas. TNIP1 knockdown significantly reduced the proliferation and migration of N33 cells（P < 0.05）. TNIP1 induced the deubiquitination of TRAF6，playing a pivotal role for NF⁃κB activation. Compared with empty vector xenografts，oe⁃TNIP1 xenografts accelerated tumor progression to a greater extent，whereas si⁃TNIP1 xenografts worked in an opposite way. Conclusion TNIP1 can induce the deubiquitination of TRAF6 protein to activate NF⁃κB，which in turn promotes the malignant progression of glioma.

Key words:

TNFα?induced protein 3?interacting protein1, nuclear factor kappa B, TNF receptor asso? ciated factor 6, glioma