文章：

GAS5通过促进E-钙黏蛋白减弱胶质瘤干细胞样细胞的恶性进展

GAS5 attenuates the malignant progression of glioma stem-like cells by promoting E-cadherin 

原文发布日期：2022-12-02 

英文摘要：

It has been widely reported that glioma stem-like cells (GSCs) serve a crucial role in the malignant progression of glioma. In particular, recent studies have reported that long non-coding RNAs (lncRNAs) are closely associated with glioma development. However, the underlying molecular regulatory mechanistic role of GSCs remains poorly understood. The present study established two highly malignant glioma stem-like cell lines from clinical surgical specimens. In these, it was found that the lncRNA growth arrest-specific 5 (GAS5) expression was downregulated in GSCs and high-grade glioma tissues, compared with normal human astrocyte cells (NHAs) and normal brain tissues, respectively, which also showed a positive correlation with patient survival. Functional assays revealed that knocking down GAS5 expression promoted the proliferation, invasion, migration, stemness, and tumorigenicity of GSGs, while suppressing their apoptosis. Mechanistically, GAS5 directly sponged miR-23a, which in turn functioned as an oncogene by inhibiting E-cadherin, through the assays of reverse transcription-quantitative PCR (RT-qPCR) and luciferase reports. In addition, rescue experiments demonstrated that GAS5 could promote the expression and function of E-cadherin in a miR-23a-dependent manner. Collectively, these data suggest that GAS5 functions as a suppressor in GSCs by targeting the miR-23a/E-cadherin axis, which may be a promising therapeutic target against glioma. 

摘要翻译： 

已有广泛报道指出，胶质瘤干细胞样细胞（GSCs）在胶质瘤恶性进展中起关键作用。特别是近期研究表明，长链非编码RNA（lncRNA）与胶质瘤发展密切相关。然而，GSCs的分子调控机制仍未被充分阐明。本研究从临床手术标本中成功建立了两株高度恶性的胶质瘤干细胞样细胞系，发现与正常人星形胶质细胞（NHAs）和正常脑组织相比，lncRNA生长停滞特异性转录本5（GAS5）在GSCs和高级别胶质瘤组织中的表达均下调，且其表达水平与患者生存率呈正相关。功能实验表明，敲低GAS5表达可促进GSCs的增殖、侵袭、迁移、干性维持和成瘤能力，同时抑制细胞凋亡。通过逆转录定量PCR（RT-qPCR）和荧光素酶报告基因检测发现，GAS5可直接吸附miR-23a，而后者通过抑制E-钙黏蛋白发挥癌基因功能。此外，挽救实验证实GAS5能以miR-23a依赖性方式促进E-钙黏蛋白的表达和功能。综上所述，这些数据表明GAS5通过靶向miR-23a/E-钙黏蛋白轴在GSCs中发挥抑癌作用，该机制可能成为胶质瘤治疗的潜在靶点。

原文链接：

GAS5 attenuates the malignant progression of glioma stem-like cells by promoting E-cadherin