研究动态
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LINC02774抑制胶质瘤中的糖酵解,通过转录因子RP58来不稳定HIF-1α。

LINC02774 inhibits glycolysis in glioma to destabilize HIF-1α dependent on transcription factor RP58.

发表日期:2023 Oct
作者: Yuanbing Chen, Yating Liu, Jianbing Xiong, Lianlian Ouyang, Miao Tang, Chao Mao, Liling Li, Desheng Xiao, Shuang Liu, Zhen Yang, Jun Huang, Yongguang Tao
来源: Epigenetics & Chromatin

摘要:

胶质瘤是脑部最常见的恶性肿瘤,是原发性脑肿瘤导致多数死亡案例的原因。长非编码RNA (lncRNA) 在HIF-1α驱动的肿瘤发展中的调控机制尚不清楚。本研究首次报道了核型长非编码RNA LINC02774。我们发现,在胶质瘤中LINC02774的表达被下调,并且随着恶性程度的增加而减少,其表达与增强磁共振相关指数(RIEMR)呈负相关。我们发现RIEMR相关的LINC02774通过调节低氧通路而不是低氧应答本身来抑制糖酵解。LINC02774与其邻近基因RP58(ZBTB18)相互作用,增强PHD3的表达,该基因可以催化HIF-1α的羟化和泛素化,从而导致HIF-1α的表达下调。我们还发现LINC02774的功能在与RP58减少时依赖于PHD3。值得注意的是,RIEMR相关的LINC02774的高表达与良好的预后相关。总之,这些发现揭示了依赖于邻近基因RP58的RIEMR相关的LINC02774在调控低氧通路中作为新型抑制肿瘤的角色,表明其有潜力成为胶质瘤的预后标志物和分子靶点治疗。© 2023 The Authors. MedComm由四川国际医药交流与促进协会(SCIMEA)和约翰威利与澳大利亚有限公司(John Wiley & Sons Australia, Ltd.)发表。
Glioma, the most common of malignant tumors in the brain, is responsible for the majority of deaths from primary brain tumors. The regulation of long noncoding RNAs (lncRNAs) in HIF-1α-driven tumor development remains unclear. LINC02774 is a nuclear lncRNA and that it is being reported for the first time in this study. We found the downregulation of LINC02774 in glioma and decreased with the degree of malignant, with its expression showing a negative correlation with the relative index of enhanced magnetic resonance (RIEMR). RIEMR-associated LINC02774 was found to inhibit glycolysis by modulating the hypoxia pathway rather than the hypoxia response itself. LINC02774 interacted with its neighboring gene, RP58 (ZBTB18), to enhance the expression of PHD3, which catalyzed HIF-1α hydroxylase and ubiquitination, leading to the downregulation of HIF-1α expression. We also found that the function of LINC02774, dependent on PHD3, was diminished upon RP58 depletion. Notably, higher expression of RIEMR-associated LINC02774 was associated with a favorable prognosis. In conclusion, these findings reveal the role of RIEMR-associated LINC02774, which relies on its neighbor gene, RP58, to regulate the hypoxia pathway as a novel tumor suppressor, suggesting its potential to be a prognostic marker and a molecular target for the therapy of glioma.© 2023 The Authors. MedComm published by Sichuan International Medical Exchange & Promotion Association (SCIMEA) and John Wiley & Sons Australia, Ltd.