Bioinformatics identification of potentially involved microRNAs in Tibetan with gastric cancer based on microRNA profiling.

Bioinformatics identification of potentially involved microRNAs in Tibetan with gastric cancer based on microRNA profiling.
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DOI:
10.1186/s12935-015-0266-1
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发表时间:
2015
影响因子:
5.8
通讯作者:
Rili G
Rili G
中科院分区:
医学2区
文献类型:
--
作者:
Luo Y;Zhang C;Tang F;Zhao J;Shen C;Wang C;Yu P;Wang M;Li Y;Di JI;Chen R;Rili G

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胃癌在藏族人群中发病率较高。本研究旨在鉴定藏族胃癌患者中差异表达的microRNAs(miRNAs),并进一步探讨其在藏族胃癌中的作用,以预测潜在的治疗靶点。选择藏族胃癌患者10例(男:女= 6:4),分离匹配的胃癌及癌旁组织标本。采用Affyscore GeneChip microRNA 3.0 Array检测样本中miRNA的表达。使用Limma软件包分析两个样品组之间的差异表达分析。然后,使用MultiMiR软件包预测miRNA的靶点。然后将目的基因导入大卫(Database for Annotation,Visualization and Integrated Discovery)数据库中,对miRNAs的重要通路进行鉴定。采用Limma软件包在R中筛选出27个差异表达的miRNA,其中25个下调(如hsa-miR-148 a-3 p、hsa-miR-148 b-3 p和hsa-miR-363- 3 p),2个上调。根据multiMiR软件包筛选出13个差异表达miRNAs的1445个靶基因(如Wnt 1、KLF 4和S1 PR 1)。其中hsa-miR-148 a-3 p、hsa-miR-148 b-3 p和hsa-miR-363- 3 p是最多的靶基因。此外,三种miRNAs在许多常见的癌症相关通路中显著富集,包括“Wnt信号通路”、“MAPK信号通路”和“Jak-STAT信号通路”。本研究发现hsa-miR-148 a-3 p、hsa-miR-148 b-3 p和hsa-miR-363- 3 p在藏族胃癌患者中表达下调,并在肿瘤相关通路中富集,可作为治疗靶点。本文的在线版本(doi:10.1186/s12935-015-0266-1)包含补充材料,可供授权用户使用。
The incidence of gastric cancer is high in Chinese Tibetan. This study aimed to identify the differentially expressed microRNAs (miRNAs) and further explore their potential roles in Tibetan with gastric cancer so as to predict potential therapeutic targets. A total of 10 Tibetan patients (male:female = 6:4) with gastric cancer were enrolled for isolation of matched gastric cancer and adjacent non-cancerous tissue samples. Affymetrix GeneChip microRNA 3.0 Array was employed for detection of miRNA expression in samples. Differential expression analysis between two sample groups was analyzed using Limma package. Then, MultiMiR package was used to predict targets for miRNAs. Following, the target genes were put into DAVID (Database for Annotation, Visualization and Integrated Discovery) to identify the significant pathways of miRNAs. Using Limma package in R, a total of 27 differentially expressed miRNAs were screened out in gastric cancer, including 25 down-regulated (e.g. hsa-miR-148a-3p, hsa-miR-148b-3p and hsa-miR-363-3p) and 2 up-regulated miRNAs. According to multiMiR package, a number of 1445 target genes (e.g. Wnt1, KLF4 and S1PR1) of 13 differentially expressed miRNAs were screened out. Among those miRNAs, hsa-miR-148a-3p, hsa-miR-148b-3p and hsa-miR-363-3p were identified with the most target genes. Furthermore, three miRNAs were significantly enriched in numerous common cancer-related pathways, including “Wnt signaling pathway”, “MAPK signaling pathway” and “Jak-STAT signaling pathway”. The present study identified a downregulation and enrichment in cancer-related pathways of hsa-miR-148a-3p, hsa-miR-148b-3p and hsa-miR-363-3p in Tibetan with gastric cancer, which can be suggested as therapeutic targets. The online version of this article (doi:10.1186/s12935-015-0266-1) contains supplementary material, which is available to authorized users.