关键词: Chronic atrophic gastritis RNA sequencing Tibetan plateau areas circRNA-miRNA-mRNA lncRNA-miRNA-mRNA

Mesh : Humans Gastritis, Atrophic / genetics Tibet RNA, Long Noncoding / genetics Gene Regulatory Networks MicroRNAs / genetics RNA, Messenger / genetics metabolism RNA, Circular / genetics Male Female Middle Aged Gene Expression Profiling Sequence Analysis, RNA Chronic Disease Ferroptosis / genetics Adult

来  源:   DOI:10.1038/s41598-024-59836-4   PDF(Pubmed)

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.
摘要:
慢性萎缩性胃炎(CAG)的发病率较高,通常被认为是胃癌(GC)的癌前病变。这项研究的目的是确定在青藏高原CAG发病的潜在分子,希望对该病的诊断和治疗有所帮助。从7例慢性胃炎(CG)患者中收集了萎缩性和非萎缩性胃粘膜组织样本。差异表达的lncRNAs,circRNAs,miRNA,基于DNBSEQ-G99RNA测序鉴定CAG和慢性非萎缩性胃炎(CNAG)组之间的mRNA。随后,构建竞争性内源性RNA(ceRNA)调控网络(lncRNA/circRNA-miRNA-mRNA网络)。两个数据集(GSE153224和GSE163416),涉及非青藏高原地区的数据,用于进一步筛选青藏高原关键mRNA,其次,还鉴定了青藏高原关键基因和与铁凋亡相关的mRNA。进行功能富集分析以研究青藏高原mRNA在CAG中的生物学功能。在这项研究中总共鉴定了七个lncRNA-miRNA-mRNA关系对和424个circRNA-miRNA-mRNA关系对。hsa_circ_0082984-hsa-miR-204-5p-CACNG8、lncRNADRAIC/has_circ_0008561-hsa-miR-34a-5p-AR/GXYLT2、lncRNAGAS1RR/RGMB-AS1/hsa_circ_00000CME41的发病机制对。此外,青藏高原关键基因和铁凋亡相关差异表达的8个常见基因(DEmRNAs)(CBS,SLC2A4,STAT3,ALOX15B,在CAG中鉴定出ATF3,IDO1,NOX4和SOCS1)。青藏高原常见的关键基因和铁凋亡相关的DMnRNAs可在JAK-STAT信号通路中发挥作用。这项研究确定了重要的分子生物标志物,这些生物标志物可能参与调节青藏高原CAG的病理机制。为今后的研究提供了潜在的研究方向。
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