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LINC01116 通过 DDX5 介导的 IL-1β 调控促进胶质瘤细胞的增殖和中性粒细胞募集。

LINC01116 promotes tumor proliferation and neutrophil recruitment via DDX5-mediated regulation of IL-1β in glioma cell.

机构信息

Department of Neurology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu Province, China.

Department of Neurology, Nanjing PuKou Central Hospital, Nanjing, Jiangsu Province, China.

出版信息

Cell Death Dis. 2020 May 1;11(5):302. doi: 10.1038/s41419-020-2506-0.

Abstract

Tumor-associated neutrophils (TANs) are important inflammatory infiltrating cells in the tumor microenvironment and are closely related to the development of human tumor. However, the underlying mechanism of TANs recruiting to glioma remains unknown. Herein, we identified that LINC01116 was significantly upregulated in glioma, and positively correlated with clinical malignancy and survival prognosis. LINC01116 regulated the progression of glioma in vitro and in vivo. RNA-seq analysis demonstrated that LINC01116 knockdown affected the expression of IL-1β, which promoted glioma proliferation and neutrophil recruitment. Furthermore, the co-culture of glioma cells and neutrophils showed that the accumulation of TANs promoted tumor proliferation via producing a host of cytokines. Mechanistically, LINC01116 activated IL-1β expression by recruiting the transcriptional regulator DDX5 to the IL-1β promoter. Our findings reveal that LINC01116 can promote glioma proliferation and neutrophil recruitment by regulating IL-1β, and may be served as a novel target for glioma therapy and prognosis.

摘要

肿瘤相关中性粒细胞(TANs)是肿瘤微环境中重要的炎症浸润细胞,与人类肿瘤的发生发展密切相关。然而,TANs 募集到神经胶质瘤中的潜在机制尚不清楚。在此,我们鉴定出 LINC01116 在神经胶质瘤中显著上调,并且与临床恶性程度和生存预后呈正相关。LINC01116 调控神经胶质瘤在体外和体内的进展。RNA-seq 分析表明,LINC01116 敲低影响了 IL-1β 的表达,从而促进了神经胶质瘤的增殖和中性粒细胞的募集。此外,神经胶质瘤细胞和中性粒细胞的共培养显示,TANs 的积累通过产生大量细胞因子促进肿瘤增殖。在机制上,LINC01116 通过募集转录调节因子 DDX5 到 IL-1β 启动子上来激活 IL-1β 的表达。我们的研究结果表明,LINC01116 可以通过调节 IL-1β 促进神经胶质瘤的增殖和中性粒细胞的募集,并且可能成为神经胶质瘤治疗和预后的新靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/58ab/7195423/0c547c8ce2e8/41419_2020_2506_Fig1_HTML.jpg

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