Pepsinogen C expression–related lncRNA/circRNA/mRNA profile and its co-mediated ceRNA network in gastric cancer

Background The expression of pepsinogen C (PGC) is considered an ideal negative biomarker of gastric cancer, but its pathological mechanisms remain unclear. This study aims to analyze competing endogenous RNA (ceRNA) networks related to PGC expression at a post-transcriptional level and build an experimental basis for studying the role of PGC in the progression of gastric cancer. Materials and methods RNA sequencing technology was used to detect the differential expression profiles of PGC-related long non-coding (lnc)RNAs, circular (circ)RNAs, and mRNAs. The online database, STRING, was used to construct protein–protein interaction (PPI) networks of differentially expressed (DE) mRNAs. A ggcorrplot R package and online database were used to construct DElncRNAs/DEcircRNAs co-mediated PGC expression–related ceRNA networks. In vivo and in vitro validations were performed using quantitative reverse transcription–PCR. Results RNA sequencing found 637 DEmRNAs, 698 DElncRNAs, and 38 DEcircRNAs. The PPI network of PGC expression–related mRNAs consisted of 503 nodes and 1179 edges. CFH, PPARG, and MUC6 directly interacted with PGC. Enrichment analysis suggested that DEmRNAs were mainly enriched in cancer-related pathways. Eleven DElncRNAs, 13 circRNAs, and 35 miRNA–mRNA pairs were used to construct ceRNA networks co-mediated by DElncRNAs and DEcircRNAs that were PGC expression–related. The network directly related to PGC was as follows: SNHG16/hsa_circ_0008197–hsa-mir-98-5p/hsa-let-7f-5p/hsa-let-7c-5p–PGC. Quantitative reverse transcriptase PCR validation results showed that PGC, PPARG, SNHG16, and hsa_circ_0008197 were differentially expressed in gastric cancer cells and tissues: PGC positively correlated with PPARG (r = 0.276, P = 0.009), SNHG16 (r = 0.35, P = 0.002), and hsa_circ_0008197 (r = 0.346, P = 0.005). Conclusion PGC-related DElncRNAs and DEcircRNAs co-mediated complicated ceRNA networks to regulate PGC expression, thus affecting the occurrence and development of gastric cancer at a post-transcriptional level. Of these, the network directly associated with PGC expression was a SNHG16/hsa_circ_0008197–mir-98-5p/hsa-let-7f-5p/hsa-let-7c-5p – PGC axis. This study may form a foundation for the subsequent exploration of the possible regulatory mechanisms of PGC in gastric cancer.

LncRNAs adjacent to pepsinogen C in gastric diseases and diagnostic efficiencies of joint detection in gastric diseases

Aims: We aimed to explore diagnostic efficiencies of long noncoding RNAs (lncRNAs) adjacent to PGC combining with sPGC and anti- Helicobacter pylori IgG in identifying GC (gastric cancer) and precancerous disease. Patients & methods: A total of 265 patients with different gastric diseases were collected. ELISA was to detect sPGC and anti- H. pylori IgG. LncRNAs was determined by qRT-PCR. Results: The area under receiver operating characteristic curve of lncRNAs in discriminating GC+AG (atrophic gastritis) and superficial gastritis (SG) were 79.0, 68.1 and 75.9%. The diagnostic performance of lncRNAs with sPGC had increasing trends in distinguishing GC from non-GC, SG from GC+AG comparing with lncRNAs, with no statistic difference. Diagnosis efficacies of lncRNAs with anti- H. pylori IgG improved dramatically. Conclusions: Serum lncRNAs could distinguish GC, AG and SG. Diagnosis efficiencies of lncRNAs with sPGC and anti- H. pylori-IgG could be improved.

mRNA and lncRNA Expression Profiling of Radiation-Induced Gastric Injury Reveals Potential Radiation-Responsive Transcription Factors

Radiation-induced gastric injury is a serious concern that may limit the duration and the delivered dose of radiation. However, the genome-wide molecular changes in stomach upon ionizing radiation have not been reported. In this study, mouse stomach was irradiated with 6 or 12 Gy X-ray irradiation and we found that radiation resulted in the atrophy of gastric mucosa and abnormal morphology of chief and parietal cells. Radiation-induced gastric injury was accompanied by an increase in the serum levels of pepsinogen A and pepsinogen C but not gastrin-17. The expression profiles of messenger RNA (mRNA) and long noncoding RNA (lncRNA) in normal and irradiated gastric tissues were measured by microarray analysis. Results revealed 17 upregulated and 10 downregulated mRNAs were consistent in 6 and 12 Gy irradiated gastric tissues, including D site-binding protein ( Dbp) and fibrinogen-like protein 1 ( Fgl1). Thirteen upregulated and 96 downregulated lncRNAs were commonly changed in 6 and 12 Gy irradiated gastric tissues. The dysregulated mRNAs were implicated in multiple pathways and showed coexpression with lncRNAs. To identify motifs for transcription factors and coactivators in the proximal promoter regions of the dysregulated RNAs, the bioinformatic tool Biopython was used. A variety of common motifs that are associated with transcription factors were identified, including ZNF263, LMX1B, and Dlx1. Our findings illustrate the molecular changes during radiation-induced gastric injury and the potential transcription factors driving this alteration.