Our objective was to determine the molecular mechanisms by which lncRNA HOXA‐AS3 regulates the biological behaviour of glioblastoma multiforme (GBM). We used an lncRNA microarray assay to identify GBM‐related lncRNA expression profiles. Qrt‐PCR was used to survey the levels of expression of long non‐coding RNA (lncRNA) HOXA‐AS3 and the target gene. Dual‐luciferase reporter assays were used to investigate the interaction of lncRNA HOXA‐AS3, the target gene and miRNA. Western blot analysis was used to examine the expression of USP3 and epithelial‐mesenchymal transition (EMT) genes. The MTT assay, transwell assay and wound healing assay were used to analyse the effects of lncRNA HOXA‐AS3 on GBM cell viability, mobility and invasiveness, respectively. Our results showed that lncRNA HOXA‐AS3 was significantly up‐regulated in GBM cells and could promote GBM cell proliferation, invasion and migration in vitro and in vivo. HOXA‐AS was found to be associated with poor survival prognosis in glioma patients. The dual‐luciferase reporter assay also revealed that lncRNA HOXA‐AS3 acts as a mir‐455‐5p sponge by up‐regulating USP3 expression to promote GBM progression. Western blot analysis showed that lncRNA HOXA‐AS3 could up‐regulate EMT‐related gene expression in GBM. Experiments showed mir‐455‐5p could rescue the effect of lncRNA HOXA‐AS3 on cell proliferation and invasion. The newly identified HOXA‐AS3/mir‐455‐5p/USP3 pathway offers important clues to understanding the key mechanisms underlying the action of lncRNA HOXA‐AS3 in glioblastoma.

中文翻译：

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LncRNA HOXA-AS3通过调节miR-455-5p / USP3轴促进胶质母细胞瘤的恶性程度。

我们的目标是确定lncRNA HOXA-AS3调节多形胶质母细胞瘤（GBM）生物学行为的分子机制。我们使用了lncRNA芯片检测法来鉴定与GBM相关的lncRNA表达谱。Qrt-PCR用于调查长非编码RNA（lncRNA）HOXA-AS3和靶基因的表达水平。使用双荧光素酶报告基因检测法研究了lncRNA HOXA-AS3，靶基因和miRNA的相互作用。蛋白质印迹分析用于检查USP3和上皮间质转化（EMT）基因的表达。使用MTT法，transwell法和伤口愈合法分别分析lncRNA HOXA-AS3对GBM细胞活力，迁移率和侵袭性的影响。我们的结果表明，lncRNA HOXA-AS3在GBM细胞中显着上调，并可以促进GBM细胞在体内外的增殖，侵袭和迁移。发现HOXA‐AS与神经胶质瘤患者的不良预后有关。双重荧光素酶报告基因检测还显示，lncRNA HOXA-AS3通过上调USP3表达以促进GBM进程而充当mir-455-5p海绵。Western blot分析表明，lncRNA HOXA-AS3可以上调GBM中与EMT相关的基因表达。实验表明，mir-455-5p可以挽救lncRNA HOXA-AS3对细胞增殖和侵袭的影响。新近鉴定出的HOXA-AS3 / mir-455-5p / USP3途径为了解lncRNA HOXA-AS3在胶质母细胞瘤中发挥作用的关键机制提供了重要线索。在体外和体内的侵袭和迁移。发现HOXA‐AS与神经胶质瘤患者的不良预后有关。双重荧光素酶报告基因检测还显示，lncRNA HOXA-AS3通过上调USP3表达以促进GBM进程而充当mir-455-5p海绵。Western blot分析表明，lncRNA HOXA-AS3可以上调GBM中与EMT相关的基因表达。实验表明，mir-455-5p可以挽救lncRNA HOXA-AS3对细胞增殖和侵袭的影响。新近鉴定出的HOXA-AS3 / mir-455-5p / USP3途径为了解lncRNA HOXA-AS3在胶质母细胞瘤中发挥作用的关键机制提供了重要线索。在体外和体内的侵袭和迁移。发现HOXA-AS与神经胶质瘤患者的不良预后有关。双重荧光素酶报告基因检测还显示，lncRNA HOXA-AS3通过上调USP3表达以促进GBM进程而充当mir-455-5p海绵。Western blot分析表明，lncRNA HOXA-AS3可以上调GBM中与EMT相关的基因表达。实验表明，mir-455-5p可以挽救lncRNA HOXA-AS3对细胞增殖和侵袭的影响。新近鉴定出的HOXA-AS3 / mir-455-5p / USP3途径为了解lncRNA HOXA-AS3在胶质母细胞瘤中发挥作用的关键机制提供了重要线索。双重荧光素酶报告基因检测还显示，lncRNA HOXA-AS3通过上调USP3表达以促进GBM进程而充当mir-455-5p海绵。Western blot分析表明，lncRNA HOXA-AS3可以上调GBM中与EMT相关的基因表达。实验表明，mir-455-5p可以挽救lncRNA HOXA-AS3对细胞增殖和侵袭的影响。新近鉴定出的HOXA-AS3 / mir-455-5p / USP3途径为了解lncRNA HOXA-AS3在胶质母细胞瘤中发挥作用的关键机制提供了重要线索。双重荧光素酶报告基因检测还显示，lncRNA HOXA-AS3通过上调USP3表达以促进GBM进程而充当mir-455-5p海绵。Western blot分析表明，lncRNA HOXA-AS3可以上调GBM中与EMT相关的基因表达。实验表明，mir-455-5p可以挽救lncRNA HOXA-AS3对细胞增殖和侵袭的影响。新近鉴定出的HOXA-AS3 / mir-455-5p / USP3途径为了解lncRNA HOXA-AS3在胶质母细胞瘤中发挥作用的关键机制提供了重要线索。