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一种系统性的框架,用于识别预后性坏死相关 lncRNAs 并验证 lncRNA CRNDE/miR-23b-3p/IDH1 调控轴在胶质瘤中的作用。

A systematic framework for identifying prognostic necroptosis-related lncRNAs and verification of lncRNA CRNDE/miR-23b-3p/IDH1 regulatory axis in glioma.

机构信息

Department of Dermatology, The First Affiliated Hospital of Jinan University, Jinan University, Guangzhou, China.

Department of Dermatology, Dermatology Hospital, Southern Medical University, Guangzhou, China.

出版信息

Aging (Albany NY). 2023 Nov 6;15(21):12296-12313. doi: 10.18632/aging.205180.

Abstract

Glioma remains the most frequent malignancy of the central nervous system. Recently, necroptosis has been identified as a cell death process that mediates the proliferation and development of tumor cells. LncRNAs play a key role in the diagnosis and treatment of various diseases. However, the impact that necrosis-related lncRNAs (NRLs) have on glioma remains unclear. In our studies, we selected 9 NRLs to construct a prognostic model. Meanwhile, we assessed the survival curves of these 9 NRLs. Our findings found ADGRA1-AS1 and WAC-AS1 were protective lncRNAs, while MIR210HG, LINC01503, CRNDE, HOXC-AS1, ZIM2-AS1, MIR22HG and PLBD1-AS1 were risk lncRNAs. Specifically, 12 immune cells, 25 immune-correlated pathways, and TME score were differentially expressed in the both risk groups. Additionally, the study predicted and validated the necroptosis-related lncRNA CRNDE/miR-23b-3p/IDH1 axis. CRNDE was strongly expressed in glioma specimens and several cell lines. Inhibiting CRNDE resulted in a substantial reduction in the proliferation and migration of U-118MG and U251 cells. Furthermore, the study predicted that CRNDE may exhibit oncogenic features by adsorbing miR-23b-3p and positively regulating IDH1 expression. Overall, the study constructed a prognostic model in glioma, and predicted a lncRNA CRNDE/miR-23b-3p/IDH1 axis, which could potentially be useful for gene therapy of glioma.

摘要

神经胶质瘤仍然是中枢神经系统最常见的恶性肿瘤。最近,坏死性凋亡已被确定为一种细胞死亡过程,介导肿瘤细胞的增殖和发育。lncRNAs 在各种疾病的诊断和治疗中发挥着关键作用。然而,坏死相关 lncRNAs(NRLs)对神经胶质瘤的影响尚不清楚。在我们的研究中,我们选择了 9 个 NRL 来构建一个预后模型。同时,我们评估了这 9 个 NRL 的生存曲线。我们的研究结果发现 ADGRA1-AS1 和 WAC-AS1 是保护性 lncRNA,而 MIR210HG、LINC01503、CRNDE、HOXC-AS1、ZIM2-AS1、MIR22HG 和 PLBD1-AS1 是风险 lncRNA。具体来说,在两个风险组中,有 12 种免疫细胞、25 种免疫相关途径和 TME 评分存在差异表达。此外,该研究预测并验证了坏死相关 lncRNA CRNDE/miR-23b-3p/IDH1 轴。CRNDE 在神经胶质瘤标本和几种细胞系中表达强烈。抑制 CRNDE 可显著减少 U-118MG 和 U251 细胞的增殖和迁移。此外,该研究预测 CRNDE 可能通过吸附 miR-23b-3p 并正向调节 IDH1 表达来表现出致癌特征。总的来说,该研究构建了神经胶质瘤的预后模型,并预测了 lncRNA CRNDE/miR-23b-3p/IDH1 轴,这可能对神经胶质瘤的基因治疗有用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2a70/10683586/7a1b7662356e/aging-15-205180-g001.jpg

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