Identification of PGC-related ncRNAs and their relationship with the clinicopathologic features of gastric cancer

Abstract

Background Pepsinogen C (PGC) is considered to be the final product of mature differentiated gastric mucosa and the expression level of PGC in gastric mucosa decreased obviously in the courses of gastric cancer (GC) development. The mechanism of the down-regulation of PGC is still unclear and needs to be excavated. This study aims to identify the PGC-related ncRNAs, which may have potential to act as PGC post-transcriptional regulator, and further explore the relationship between these ncRNAs and clinicopathological parameters of GC. Methods Bioinformatics software was used to predict the target binding miRNAs for PGC and target binding circRNAs for candidate miRNAs. Dual-luciferase reporter assay was performed to validate the targeted complete complementary relationship. QRT-PCR was applied to detect the expression levels of PGC and PGC-related ncRNAs in GC tissues. Kaplan-Meier and Cox regression were used for the analysis of the relationship between these ncRNAs and prognostic significance of GC Results Hsa-let-7c was predicted to binding to PGC gene, hsa_circ_0001483 and hsa_circ_0001324 were targeted binding to hsa-let-7c, which was verified by dual-luciferase reporter assay. The hsa_circ_0001483 / hsa_circ_0001324 -hsa-let-7c-PGC axis was confirmed in GC tissues by qRT-PCR. The expression of hsa_circ_0001483 was correlated with peritumoral inflammatory cell infiltration level and lymphatic metastasis. Conclusions Hsa_circ_0001483, hsa_circ_0001324 and let-7c were newly identified and validated as PGC-related ncRNAs and were associated with the clinicopathological features of GC in some ways. The hsa_circ_0001483 / hsa_circ_0001324-hsa-let-7c-PGC axis was existed in GC, which may explain the downregulation of PGC in GC tissues.