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长链基因间非编码RNA LINC00657通过充当miR-190a-3p的分子海绵来调控胶质母细胞瘤的肿瘤发生。

Long intergenic non-coding LINC00657 regulates tumorigenesis of glioblastoma by acting as a molecular sponge of miR-190a-3p.

作者信息

Chu Liangzhao, Yu Lei, Liu Jian, Song Shibin, Yang Hua, Han Feng, Liu Fen, Hu Yaxin

机构信息

Department of Neurosurgery, Hospital affiliated to Guizhou Medical University, Guiyang 550004, Guizhou, China.

Prenatal Diagnosis Center, Hospital affiliated to Guizhou Medical University, Guiyang 550004, Guizhou, China.

出版信息

Aging (Albany NY). 2019 Mar 5;11(5):1456-1470. doi: 10.18632/aging.101845.

Abstract

To detect the aberrantly expressed long non-coding RNAs in glioblastoma, two pairs of glioblastoma and adjacent normal tissues were firstly analyzed by RNA sequencing. Long intergenic non-coding RNA LINC00657 was considered to play a vital role in glioblastoma based on the results of RNA sequencing. Hence, we aimed to investigate the mechanisms by which LINC00657 regulated the tumorigenesis of glioblastoma. The level of LINC00657 in 40 glioblastoma samples and glioblastoma cell lines was detected by RT-qPCR. LINC00657 was significantly decreased in patients with glioblastoma compared with adjacent normal tissues. Overexpression of LINC00657 inhibited proliferation, colony formation, invasion and migration in glioma cells via inducing apoptosis. Dual luciferase report assay indicated LINC00657 was the target of miR-190a-3p. Overexpression of LINC00657 greatly inhibited the relative amount of miR-190a-3p. Besides, miR-190a-3p was found to be a negative regulator of PTEN. Additionally, active-caspase 3 was increased in cells transfected with pcDNA3.1-LINC00657. Finally, results were further confirmed by studies using nude mice bearing with glioblastoma tumors. In conclusion, LINC00657 was effective in inhibiting glioblastoma by acting as a molecular sponge of miR-190a-3p to regulate PTEN expression. Therefore, targeting LINC00657 may serve as a potential strategy for the treatment of patients with glioblastoma.

摘要

为了检测胶质母细胞瘤中异常表达的长链非编码RNA,首先对两对胶质母细胞瘤组织和相邻正常组织进行了RNA测序分析。基于RNA测序结果,长链基因间非编码RNA LINC00657被认为在胶质母细胞瘤中起着至关重要的作用。因此,我们旨在研究LINC00657调控胶质母细胞瘤肿瘤发生的机制。通过RT-qPCR检测了40例胶质母细胞瘤样本和胶质母细胞瘤细胞系中LINC00657的水平。与相邻正常组织相比,胶质母细胞瘤患者中LINC00657显著降低。LINC00657的过表达通过诱导凋亡抑制胶质瘤细胞的增殖、集落形成、侵袭和迁移。双荧光素酶报告基因检测表明LINC00657是miR-190a-3p的靶标。LINC00657的过表达显著抑制了miR-190a-3p的相对含量。此外,发现miR-190a-3p是PTEN的负调控因子。另外,在转染了pcDNA3.1-LINC00657的细胞中,活化的半胱天冬酶-3增加。最后,使用携带胶质母细胞瘤肿瘤的裸鼠进行的研究进一步证实了结果。总之,LINC00657通过作为miR-190a-3p的分子海绵来调节PTEN表达,从而有效抑制胶质母细胞瘤。因此,靶向LINC00657可能是治疗胶质母细胞瘤患者的一种潜在策略。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7018/6428093/57fb376f0e7f/aging-11-101845-g001.jpg

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