Exploration of lncRNA/circRNA-miRNA-mRNA network in patients with chronic atrophic gastritis in Tibetan plateau areas based on DNBSEQ-G99 RNA sequencing

Abstract

A higher incidence of chronic atrophic gastritis (CAG) is generally considered as a precancerous lesion in gastric cancer (GC). The aim of this study was to identify potential molecules involved in the pathogenesis of CAG in the Tibetan plateau, hoping to help the diagnosis and management of the disease. Atrophic and non-atrophic gastric mucosal tissue samples were collected from seven patients with chronic gastritis (CG). Differentially expressed lncRNAs, circRNAs, miRNAs, and mRNAs between CAG and chronic non-atrophic gastritis (CNAG) groups were identified based on DNBSEQ-G99 RNA sequencing. Subsequently, competitive endogenous RNA (ceRNA) regulatory networks (lncRNA/circRNA-miRNA-mRNA networks) were constructed. Two datasets (GSE153224 and GSE163416), involving data from non-Tibetan plateau areas, were used to further screen out Tibetan plateau key mRNAs, followed by the common genes of Tibetan plateau key and ferroptosis-related mRNAs were also identified. Functional enrichment analyses were performed to investigate the biological functions of Tibetan plateau mRNAs in the CAG. A total of seven lncRNA-miRNA-mRNA relationship pairs and 424 circRNA-miRNA-mRNA relationship pairs were identified in this study. The relationship pairs of hsa_circ_0082984-hsa-miR-204-5p-CACNG8, lncRNA DRAIC/has_circ_0008561-hsa-miR-34a-5p-AR/GXYLT2, lncRNA GAS1RR/RGMB-AS1/hsa_circ_0008561-hsa-miR-3614-5p-TMEM216/SUSD5, and LINC00941/hsa_circ_0082984-hsa-miR-873-3p-TMC5 can be involved in the pathogenesis of CAG. Additionally, eight common genes of Tibetan plateau key and ferroptosis-related differentially expressed mRNAs (DEmRNAs) (CBS, SLC2A4, STAT3, ALOX15B, ATF3, IDO1, NOX4, and SOCS1) were identified in CAG. The common genes of Tibetan plateau key and ferroptosis-related DEmRNAs can play a role in the JAK-STAT signaling pathway. This study identified important molecular biomarkers that may be involved in regulating the pathological mechanisms of CAG in the Tibetan plateau, which provides potential research directions for future research.

Keywords: Chronic atrophic gastritis; RNA sequencing; Tibetan plateau areas; circRNA-miRNA-mRNA; lncRNA-miRNA-mRNA.

Figure 1

The flowchart of this study.

Figure 2

Volcano plots and heatmaps of DEmRNAs, DEmiRNAs, DElncRNAs, and DEcircRNAs between CAG and CNAG groups. (A–D) The volcano plots of DEmRNAs/DEmiRNAs/DElncRNAs/DEcircRNAs. Red dots represents up-regulated in the CAG group. Blue dots represents down-regulated in the CAG group. (E–H) The heatmaps of DEmRNAs/DEmiRNAs/DElncRNAs/DEcircRNAs. Red represents up-regulated, blue represents down-regulated. CAG chronic atrophic gastritis; CNAG chronic non-atrophic gastritis.

Figure 3

Visualization of lncRNA target mRNAs prediction in CAG and CNAG groups. Pink represents up-regulated, green represents down-regulated. Circles represents mRNAs, rhombuses represents lncRNAs. CAG chronic atrophic gastritis; CNAG chronic non-atrophic gastritis.

Figure 4

The ceRNA network of lncRNA-miRNA-mRNA in CAG and CNAG groups. Pink represents up-regulated, blue represents down-regulated. Rectangles represents mRNAs, triangles represents miRNAs, V-shaped represents lncRNAs. CAG chronic atrophic gastritis; CNAG chronic non-atrophic gastritis.

Figure 5

The ceRNA network of circRNA-miRNA-mRNA in CAG and CNAG groups. Pink represents up-regulated, blue represents down-regulated. Rectangles represents mRNAs, triangles miRNAs, rhombuses represents circRNAs. CAG chronic atrophic gastritis; CNAG chronic non-atrophic gastritis.

Figure 6

Venn diagrams of DEmRNAs (A) and DElncRNAs (B) between Tibetan plateau areas and non-Tibetan plateau areas in CAG and CNAG groups. CAG chronic atrophic gastritis; CNAG chronic non-atrophic gastritis.

Figure 7

KEGG and GO enrichment analysis of DEmRNAs between CAG and CNAG groups in the Tibetan plateau areas. (A, B) KEGG and GO enrichment analysis of DEmRNAs in mRNA-miRNA-lncRNA network; (C) GO enrichment analysis of DEmRNAs in mRNA-miRNA-circRNA network; (D, E) KEGG and GO enrichment analysis of Tibetan plateau key DEmRNAs; (F, G) KEGG and GO enrichment analysis of common genes of Tibetan plateau key and ferroptosis related DEmRNAs. CAG chronic atrophic gastritis; CNAG chronic non-atrophic gastritis; KEGG Kyoto encyclopedia of genes and genomes; GO gene ontology.