Objective Cytotoxin associated protein A (CagA), the main virulence factor of Helicobacter pylori (Hp), plays an important role in the occurrence and development of gastric cancer. Micro RNA (miRNA) can promote or inhibit cancer by affecting the expression of downstream mRNA molecules. The aim of the study is to explore CagA-related miRNAs and effects of the miRNAs on gastric cancer for providing evidences to the diagnosis and treatment of gastric cancer correlated with Hp-CagA infection.
Methods MiRNAs related to both Hp infection and gastric cancer were screened in the Gene Expression Omnibus (GEO) database and relevant clinicopathological data were analyzed based on the Cancer Genome Atlas (TCGA) dataset. The prokaryotic expression system of CagA was constructed and AGS cells were transfected with different concentrations of CagA. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to detect the expression of the targeted miRNAs after transfection. Finally, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis of the miRNA were predicted and analyzed with DIANAmirpath3.0 online websites.
Results MiR-142-3p was confirmed being related Hp- CagA infection based on GEO database, TCGA dataset and cell experiment. In clinical studies, mir-142 expression was associated with the prognosis of male patients with stage I gastric cancer and female patients aged 45 – 54 and 55 – 64 years (all P < 0.05). In cytological studies, the expression of miR-142-3p was up-regulated in gastric cancer cells (P < 0.01) and the level of miR-142-3p expression was affected by Hp- CagA infection (P < 0.01). Other study results suggested that as downstream targets, phosphoinositide-3-kinase regulatory subunit 2 (PIK3R2), PIK3R5 and phosphoinositide-3 kinase, catalytic subunit delta (PIK3CD) may be closely related to the effect of miR-142-3p in progressing course of gastric cancer.
Conclusion MiR-142-3p may promote gastric cancer progressing through pathways of PIK3R2/PIK3R5/PIK3CD and may be a potential therapeutic target.
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