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长链非编码 RNA LINC00319 与胶质瘤的发生发展和不良预后相关。

LncRNA LINC00319 is associated with tumorigenesis and poor prognosis in glioma.

机构信息

Department of Radiology, The First Affiliated Hospital of Xinxiang Medical University, Xinxiang, Henan, 453100, China.

Magnetic Resonance Imagine Department, The First Affiliated Hospital of Xinxiang Medical University, Xinxiang, Henan, 453100, China.

出版信息

Eur J Pharmacol. 2019 Oct 15;861:172556. doi: 10.1016/j.ejphar.2019.172556. Epub 2019 Jul 17.

DOI:10.1016/j.ejphar.2019.172556
PMID:31325436
Abstract

Glioma is one of the most universally diagnosed malignant tumors in the central nervous system with high mortality and morbidity in the world. Long non-coding long intergenic non-protein coding RNA 319 (LINC00319) exerts promoting function in diverse range of human carcinomas, but its detailed role in glioma remains to be investigated. This study aimed to investigate the potential role and regulatory mechanism of LINC00319 and also its clinical value in glioma. In our study, LINC00319 was expressed at high levels in glioma and closely associated with poor prognosis of patients with glioma, whose knockdown impaired cell proliferation, arrested cell cycle and induced cell apoptosis of glioma. In addition, high expression of high mobility group AT-hook 2 (HMGA2) was found in glioma which was also in positive relation to LINC00319 expression. Moreover, LINC00319 directly bound to TATA-box binding protein associated factor 1 (TAF1) and further regulated HMGA2. Finally, rescue assays verified that LIN00319 modulated the tumorigenesis of glioma by regulating HMGA2. The present research elucidated the function role and underlying mechanism of LINC00319 in glioma and exposed a new insight into the molecular-targeted therapy for glioma.

摘要

神经胶质瘤是中枢神经系统中最普遍诊断的恶性肿瘤之一,在世界范围内死亡率和发病率都很高。长非编码 RNA 长基因间非蛋白编码 RNA 319(LINC00319)在多种人类癌中发挥促进作用,但它在神经胶质瘤中的详细作用仍有待研究。本研究旨在探讨 LINC00319 的潜在作用和调节机制及其在神经胶质瘤中的临床价值。在我们的研究中,LINC00319 在神经胶质瘤中表达水平较高,与神经胶质瘤患者的预后不良密切相关,其敲低可损害神经胶质瘤细胞的增殖,阻滞细胞周期并诱导细胞凋亡。此外,在神经胶质瘤中发现高迁移率族蛋白 A2(HMGA2)表达较高,与 LINC00319 的表达呈正相关。此外,LINC00319 直接与 TATA 盒结合蛋白相关因子 1(TAF1)结合,并进一步调节 HMGA2。最后,挽救实验验证了 LINC00319 通过调节 HMGA2 来调节神经胶质瘤的肿瘤发生。本研究阐明了 LINC00319 在神经胶质瘤中的功能作用及其潜在机制,为神经胶质瘤的分子靶向治疗提供了新的思路。

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