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长链非编码 RNA TRG-AS1 通过与 miR-877-5p 竞争结合来调节 SUZ12 表达,从而促进神经胶质瘤细胞增殖。

LncRNA TRG-AS1 promotes glioblastoma cell proliferation by competitively binding with miR-877-5p to regulate SUZ12 expression.

机构信息

Department of Neurosurgery, Fujian Medical University Union Hospital, No.29 Xinquan Road, Fuzhou, Fujian, 350001, China.

Department of Neurosurgery, Fujian Medical University Union Hospital, No.29 Xinquan Road, Fuzhou, Fujian, 350001, China.

出版信息

Pathol Res Pract. 2019 Aug;215(8):152476. doi: 10.1016/j.prp.2019.152476. Epub 2019 May 28.

DOI:10.1016/j.prp.2019.152476
PMID:31196742
Abstract

Glioblastoma is one of the most fatal diseases in human central nerve system. However, the prognosis and treatment of glioblastoma still call for steady improvement. In recent years, increasing studies have revealed that the abnormal expression of long non-coding RNA (lncRNA) is closely related to carcinogenesis and prognosis. Unfortunately, many lncRNAs still need further research in their function and molecule mechanism. LncRNA TRG-AS1 hasn't been detected in any types of cancers before. TRG-AS1 is associated with poor prognosis and is upregulated in glioblastoma tissues and cells. TRG-AS1 can also accelerate glioblastoma cell proliferation in return. On the other hand, miRNA-877-5p expresses low in glioblastoma and contains binding sites with both TRG-AS1 and SUZ12. Furthermore, TRG-AS1 suppresses the expression of miR-877-5p while miR-877-5p suppresses SUZ12 expression. Overexpression of TRG-AS1 could promote the expression of SUZ12.Rescue assays demonstrates that overexpression of SUZ12 can counteract the decline of glioblastoma cell proliferation induced by knockdown of TRG-AS1. Based on all these assays, TRG-AS1 promotes glioblastoma cell proliferation by acting as a ceRNA of miR-877-5p to regulate SUZ12 expression. TRG-AS1 might serve as a new target in glioblastoma treatment.

摘要

胶质母细胞瘤是人类中枢神经系统中最致命的疾病之一。然而,胶质母细胞瘤的预后和治疗仍需要不断改善。近年来,越来越多的研究表明,长链非编码 RNA(lncRNA)的异常表达与致癌和预后密切相关。不幸的是,许多 lncRNA 的功能和分子机制仍需要进一步研究。TRG-AS1 以前从未在任何类型的癌症中检测到。TRG-AS1 与预后不良有关,在胶质母细胞瘤组织和细胞中上调。TRG-AS1 还可以反过来加速胶质母细胞瘤细胞的增殖。另一方面,miR-877-5p 在胶质母细胞瘤中表达较低,并且与 TRG-AS1 和 SUZ12 都有结合位点。此外,TRG-AS1 抑制 miR-877-5p 的表达,而 miR-877-5p 抑制 SUZ12 的表达。TRG-AS1 的过表达可以促进 SUZ12 的表达。挽救实验表明,过表达 SUZ12 可以抵消 TRG-AS1 敲低诱导的胶质母细胞瘤细胞增殖的下降。基于所有这些实验,TRG-AS1 通过作为 miR-877-5p 的 ceRNA 来调节 SUZ12 的表达,从而促进胶质母细胞瘤细胞的增殖。TRG-AS1 可能成为胶质母细胞瘤治疗的新靶点。

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