Integrative Analysis of Differential lncRNA/mRNA Expression Profiling in Helicobacter pylori Infection-Associated Gastric Carcinogenesis
Integrative Analysis of Differential lncRNA/mRNA Expression Profiling in Helicobacter pylori Infection-Associated Gastric Carcinogenesis
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幽门螺杆菌感染相关胃癌发生中差异 lncRNA/mRNA 表达谱的综合分析
DOI：
10.3389/fmicb.2020.00880
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发表时间：
2020-05-08
影响因子：
5.2
通讯作者：
Lu, Nong-Hua
中科院分区：
文献类型：
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作者：
Li, Nianshuang;Ouyang, Yaobin;Lu, Nong-Hua
幽门螺杆菌（H.幽门螺杆菌）感染是胃癌（GC）的最大已知危险因素。长链非编码RNA（lncRNA）参与多种生物学过程。然而，他们在H.幽门相关性胃癌仍是未知数。我们进行了转录组测序，以研究差异lncRNA和mRNA表达谱在胃AGS细胞感染H。pylori菌株7.13或43504。我们鉴定了H.幽门感染通过WGCNA分析构建lncRNA和mRNA的共表达网络。此外，选择了几个最显著上调的基因用于在H. pylori感染的胃细胞和转基因INS-GAS小鼠。最后，我们评估了这些基因在人类胃癌组织。在未感染和感染细胞之间共鉴定出158442个基因。其中，298个mRNA和73个lncRNA在感染H. pylori 7.13株和43504株。通过qRT-PCR分析验证了大多数上调mRNA（DDIT 4、NDRG 1、CHAC 1、IL 32、RELB、CTH和SLC7A1）和lncRNA（lncRNA36068、lncRNA51663、lncRNA49853、lncRNA49852和FLJ46906）的表达水平。我们发现H. pylori感染显著诱导了RELB和SLC7A11编码基因在体外和体内的转录水平，这得到了它们在GC组织中的高表达水平的支持。此外，lncRNA51663和FLJ46906在H. pylori感染的细胞，并且与邻近的正常组织相比，在人GC组织中持续过表达。我们的研究确定了与H.幽门感染这些结果可能提供重要的见解lncRNA在H。幽门诱发胃癌
Helicobacter pylori (H. pylori) infection is the greatest known risk factor for gastric cancer (GC). Long non-coding RNAs (lncRNAs) are implicated in multiple biological processes. However, their contribution in H. pylori-associated GC remains largely unknown. We performed transcriptome sequencing to investigate differential lncRNA and mRNA expression profiles in gastric AGS cells infected with the H. pylori strain 7.13 or 43504. We identified significantly differentially expressed (SDE) mRNAs and lncRNAs following H. pylori infection. A co-expression network of lncRNAs and mRNAs was constructed via WGCNA analysis. Moreover, several of the most significantly upregulated genes were selected for further validation by qRT-PCR analysis in H. pylori-infected gastric cells and transgenic INS-GAS mice. We finally evaluated these genes in human GC tissues. A total of 158442 genes were identified between uninfected and infected cells. Of these, 298 mRNAs and 73 lncRNAs were consistently differentially expressed following infection with the H. pylori 7.13 and 43504 strains, respectively. The expression levels of most upregulated mRNAs (DDIT4, NDRG1, CHAC1, IL32, RELB, CTH, and SLC7A1) and lncRNAs (lncRNA36068, lncRNA51663, lncRNA49853, lncRNA49852, and FLJ46906) were validated by qRT-PCR analysis. We found that H. pylori infection significantly induced the transcript levels of the coding genes RELB and SLC7A11 in in vitro and in vivo assays, which was supported by their high expression levels in GC tissues. In addition, lncRNA51663 and FLJ46906 were remarkably increased in H. pylori-infected cells and consistently overexpressed in human GC tissues compared to adjacent normal tissues. Our study identified mRNA and lncRNA expression profiles related to H. pylori infection. These results may provide important insights regarding lncRNAs in H. pylori-induced gastric carcinogenesis.