Integrative Analysis of Differential lncRNA/mRNA Expression Profiling in Helicobacter pylori Infection-Associated Gastric Carcinogenesis.

Nianshuang Li,Junbo Hong,Yin Zhu,Nong-Hua Lu,Cong He,Chao Peng,Xiaoyu Yang,Sihai Chen,Yaobin Ouyang

doi:10.3389/fmicb.2020.00880

Nianshuang Li, Junbo Hong + Show 7 more

Open Access

https://doi.org/10.3389/fmicb.2020.00880

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Abstract

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.

Highlights

It is steadily declining in incidence, gastric cancer (GC) is still the third leading cause of cancer deaths worldwide
To identify mRNA and Long non-coding RNAs (lncRNAs) expression profiles correlated with H. pylori infection, AGS gastric epithelial cells were cocultured with H. pylori 43504 or 7.13
In response to H. pylori infection, non-coding RNAs were dysregulated to promote oncogenic cellular processes, which augments the progression to gastric carcinogenesis (Yousefi et al, 2019). lncRNAs, as unique noncoding RNAs, are the key regulators of genes in different physiological and pathological processes

Summary

Introduction

It is steadily declining in incidence, gastric cancer (GC) is still the third leading cause of cancer deaths worldwide. An infection with the gram-negative microaerophilic bacterium Helicobacter pylori (H. pylori) has been identified as a group I carcinogen by the IARC/WHO. Most individuals infected with H. pylori are asymptomatic. Only 10–15% of individuals infected with H. pylori develop duodenal ulcer diseases, and 1–3% of individuals are estimated to develop GC (Li et al, 2018). We have previously shown that the release of ROS, the DNA damage response, and the inflammatory response are increased in gastric epithelial cells infected with H. pylori (Xie et al, 2018; Hu et al, 2019). Many randomized controlled trials have indicated that eradication of H. pylori can significantly reduce the risk of GC (Li et al, 2014; Li et al, 2019). Different pathogenic mechanisms of gastric carcinogenesis have been identified in multiple studies, the underlying molecular mechanism remains unknown

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