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mir-196a-5p在胃癌中的上调及其靶基因的KEGG通路富集分析的临床意义

Clinical significance of upregulation of mir-196a-5p in gastric cancer and enriched KEGG pathway analysis of target genes.

作者信息

Li Hai-Long, Xie Shou-Pin, Yang Ya-Li, Cheng Ying-Xia, Zhang Ying, Wang Jing, Wang Yong, Liu Da-Long, Chen Zhao-Feng, Zhou Yong-Ning, Wu Hong-Yan

机构信息

Department of Clinical Testing Teaching and Research, School of Medical Technology, Gansu Traditional Chinese Medical University, Lanzhou, China E-mail :

出版信息

Asian Pac J Cancer Prev. 2015;16(5):1781-7. doi: 10.7314/apjcp.2015.16.5.1781.

Abstract

BACKGROUND

miRNAs are relatively recently discovered cancer biomarkers which have important implications for cancer early diagnosis, treatment and estimation of prognosis. Here we focussed on expression of mir-196a-5p in gastric cancer tissues and cell lines so as to analyse its significance for clinicopathologic characteristics and generate enriched KEGG pathways clustered by target genes for exploring its potential roles as a biomarker in gastric cancer.

MATERIALS AND METHODS

The expression of mir-196a-5p in poorly, moderate and well differentiated gastric cancer cell lines compared with GES-1 was detected by RT-qPCR, and the expression of mir-196a-5p in gastric cancer tissues comparing with adjacent non cancer tissues of 58 cases were also assessed by RT- qPCR. Subsequently, an analysis of clinical significance of mir-196a-5p in gastric cancer and enriched KEGG pathways was executed based on the miRWalk prediction database combined with bioinformatics tools DAVID 6.7 and Mirfocus 3.0.

RESULTS

RT-qPCR showed that mir-196a-5p was up-regulated in 6 poorly and moderate differentiated gastric cancer cell lines SGC-7901, MKN-45, MKN-28, MGC-803, BGC-823, HGC-27 compared with GES-1, but down-regulated in the highly differentiated gastric cancer cell line AGS. Clinical data indicated mir-196a-5p to beup-regulated in gastric cancer tissues (47/58). Overexpression of mir-196a-5p was associated with more extensive degree of lymph node metastasis and clinical stage (P <0.05; x2 test). Enriched KEGG pathway analyses of predicted and validated targets in miRWalk combined with DAVID 6.7 and Mirfocus 3.0 showed that the targeted genes regulated by mir-196a-5p were involved in malignancy associated biology.

CONCLUSIONS

Overexpression of mir-196a-5p is associated with lymph node metastasis and clinical stage, and enriched KEGG pathway analyses showed that targeted genes regulated by mir-196a-5p may contribute to tumorgenesis, suggesting roles as an oncogenic miRNA biomarker in gastric cancer.

摘要

背景

微小RNA(miRNAs)是近年来发现的癌症生物标志物,对癌症的早期诊断、治疗及预后评估具有重要意义。在此,我们聚焦于mir-196a-5p在胃癌组织和细胞系中的表达,以分析其对临床病理特征的意义,并生成由靶基因聚类的富集KEGG通路,从而探索其作为胃癌生物标志物的潜在作用。

材料与方法

采用逆转录定量聚合酶链反应(RT-qPCR)检测低分化、中分化和高分化胃癌细胞系相较于GES-1中mir-196a-5p的表达情况,同时也通过RT-qPCR评估58例胃癌组织中mir-196a-5p的表达,并与相邻非癌组织进行比较。随后,基于miRWalk预测数据库,结合生物信息学工具DAVID 6.7和Mirfocus 3.0,对mir-196a-5p在胃癌中的临床意义及富集的KEGG通路进行分析。

结果

RT-qPCR结果显示,与GES-1相比,6种低分化和中分化胃癌细胞系SGC-7901、MKN-45、MKN-28、MGC-803、BGC-823、HGC-27中mir-196a-5p表达上调,但在高分化胃癌细胞系AGS中表达下调。临床数据表明,mir-196a-5p在胃癌组织中表达上调(47/58)。mir-196a-5p的过表达与更广泛的淋巴结转移程度和临床分期相关(P<0.05;卡方检验)。结合DAVID 6.7和Mirfocus 3.0对miRWalk中预测和验证的靶标进行富集KEGG通路分析,结果显示mir-196a-5p调控的靶基因参与了与恶性肿瘤相关的生物学过程。

结论

mir-196a-5p的过表达与淋巴结转移和临床分期相关,富集KEGG通路分析表明mir-196a-5p调控的靶基因可能促进肿瘤发生,提示其作为胃癌致癌性微小RNA生物标志物的作用。

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