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爱泼斯坦-巴尔病毒miR-BART17-5p通过靶向胃癌中的Kruppel样因子2促进迁移和锚定非依赖性生长。

Epstein-Barr Virus miR-BART17-5p Promotes Migration and Anchorage-Independent Growth by Targeting Kruppel-Like Factor 2 in Gastric Cancer.

作者信息

Yoon Jae Hee, Min Kyoungmi, Lee Suk Kyeong

机构信息

Department of Medical Life Sciences, Department of Biomedicine & Health Sciences, College of Medicine, The Catholic University of Korea, Seoul 06591, Korea.

出版信息

Microorganisms. 2020 Feb 15;8(2):258. doi: 10.3390/microorganisms8020258.

Abstract

Epstein-Barr virus (EBV) infects more than 90% of the global population and is associated with a variety of tumors including nasopharyngeal carcinoma, Hodgkin lymphoma, natural killer/T lymphoma, and gastric carcinoma. In EBV-associated gastric cancer (EBVaGC), highly expressed EBV BamHI A rightward transcripts (BART) miRNAs may contribute to tumorigenesis with limited viral antigens. Despite previous studies on the targets of BART miRNAs, the functions of all 44 BART miRNAs have not been fully clarified. Here, we used RNA sequencing data from the Cancer Genome Atlas to find genes with decreased expression in EBVaGC. Furthermore, we used AGS cells infected with EBV to determine whether expression was reduced by BART miRNA. We showed that the expression of Kruppel-like factor 2 () is lower in AGS-EBV cells than in the AGS control. Using bioinformatics analysis, four BART miRNAs were selected to check whether they suppress expression. We found that only miR-BART17-5p directly down-regulated and promoted gastric carcinoma cell migration and anchorage-independent growth. Our data suggest that functions as a tumor suppressor in EBVaGC and that miR-BART17-5p may be a valuable target for effective EBVaGC treatment.

摘要

爱泼斯坦-巴尔病毒(EBV)感染了全球90%以上的人口,并与多种肿瘤相关,包括鼻咽癌、霍奇金淋巴瘤、自然杀伤/T细胞淋巴瘤和胃癌。在EBV相关胃癌(EBVaGC)中,高表达的EBV BamHI A向右转录本(BART)miRNA可能在病毒抗原有限的情况下促进肿瘤发生。尽管之前对BART miRNA的靶标进行了研究,但44种BART miRNA的功能尚未完全阐明。在此,我们利用癌症基因组图谱的RNA测序数据来寻找在EBVaGC中表达降低的基因。此外,我们使用感染了EBV的AGS细胞来确定BART miRNA是否会降低其表达。我们发现,AGS-EBV细胞中Kruppel样因子2()的表达低于AGS对照细胞。通过生物信息学分析,选择了4种BART miRNA来检测它们是否抑制 表达。我们发现只有miR-BART17-5p直接下调 并促进胃癌细胞迁移和非锚定依赖性生长。我们的数据表明, 在EBVaGC中发挥肿瘤抑制作用,而miR-BART17-5p可能是有效治疗EBVaGC的一个有价值的靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a95a/7074886/bc4c830248e6/microorganisms-08-00258-g001.jpg

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