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miR‐505 acts as a tumor suppressor in gastric cancer progression through targeting HMGB1

机译:MiR-505通过靶向HMGB1作为胃癌进展中的肿瘤抑制剂

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Abstract Gastric cancer (GC) is a frequent type of malignant tumor worldwide. GC metastasis results in the majority of clinical treatment failures. MicroRNAs (miRNA) are identified to exhibit crucial roles in GC. Our current study aimed to explore the biological roles of miR‐505 in GC progression. It was observed that miR‐505 was robustly decreased in GC cells compared with human normal gastric epithelial GES‐1 cells. Overexpression of miR‐505 was able to repress GC progression in AGS and BGC‐823 cells. In addition, high‐mobility group box 1 (HMGB1) has been identified as a crucial oncogene in several cancer types. By carrying out bioinformatics analysis, HMGB1 was predicted as a direct target of miR‐505. Meanwhile, HMGB1 was found to be significantly increased in GC cells and it was confirmed in our study that miR‐505 can directly target HMGB1 in vitro. miR‐505 mimics can inhibit HMGB1 messenger RNA and protein expression dramatically. Subsequently, knockdown of HMGB1 can inhibit GC cell proliferation, colony formation, and induce cell apoptosis. Furthermore, HMGB1 silence suppressed GC cell migration and invasion greatly in vitro. Finally, it was validated that miR‐505 can inhibit GC progression by targeting HMGB1 in vivo. Taken these together, it was indicated that miR‐505/HMGB1 axis was involved in the development of GC. miR‐505 can serve as a potential prognostic indicator in GC therapy.
机译:摘要胃癌(GC)是全世界常见的恶性肿瘤。 GC转移导致大多数临床治疗失败。鉴定MicroRNAs(miRNA)以表现在GC中的重要作用。我们目前的研究旨在探讨MIR-505在GC进展中的生物学作用。观察到,与人正常胃上皮GES-1细胞相比,MIR-505在GC细胞中鲁棒地降低。 miR-505的过度表达能够在AGS和BGC-823细胞中压制GC进展。此外,高迁移率组盒1(HMGB1)已被鉴定为几种癌症类型中的关键癌基因。通过进行生物信息学分析,预测HMGB1作为miR-505的直接目标。同时,在GC细胞中发现HMGB1显着增加,我们在我们的研究中证实MIR-505可以直接靶向HMGB1。 miR-505模拟可以急剧抑制HMGB1信使RNA和蛋白质表达。随后,HMGB1的敲低可以抑制GC细胞增殖,菌落形成和诱导细胞凋亡。此外,HMGB1沉默抑制了GC细胞迁移和体外侵袭。最后,经过验证,MIR-505可以通过靶向体内HMGB1来抑制GC进展。将这些带在一起,表示MiR-505 / HMGB1轴涉及GC的开发。 miR-505可以作为GC疗法中的潜在预后指标。

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