Helicobacter pylori Accelerates the Occurrence and Development of Gastric Adenocarcinomas by Regulating the MiR-146a-5p/FHL1 Axis

Abstract

Background: Gastric cancer (GC) is a common malignancy of the digestive tract and about 95% of them are gastric adenocarcinomas (STAD). However, Helicobacter pylori (HP) infection does not only serve as a major risk factor for GC but is also linked to the differential expression of miRNAs. Moreover, miR-146a-5p has a crucial role in numerous human malignancies. Therefore, this study aimed to explore the molecular mechanisms underlying the role of miR-146a-5p in HP-associated STAD. Methods: MiRNAs genes linked to HP-induced GC were retrieved from the GeneCards and g: Profiler databases. MiR-146a-5p expression in HP-induced STAD was determined using quantitative real-time PCR. The role of miR-146a-5p in HP-induced STAD was assessed using Cell Counting Kit-8, colony formation assay, wound healing analysis, transwell analysis, flow cytometry, and Western blot. Furthermore, the mechanism of miR-146a-5p in STAD was evaluated using a dual-luciferase reporter assay. Results: MiR-146a-5p expression was significantly increased in HP-infected STAD cells. Moreover, HP infection promoted STAD cell growth by increasing the expression of miR-146a-5p. Mechanistically, miR-146a-5p targeted four-and-a-half LIM domain protein 1 (FHL1), and rescue assays further authenticated that HP facilitated STAD cell growth by increasing miR-146a-5p to reduce FHL1. Conclusion: In summary, HP infection leads to elevated miR-146a-5p expression and promotes STAD by mediating the miR-146a-5p/FHL1 pathway. This study might provide a basis for considering miR-146a-5p as a diagnostic marker for STAD and may help in designing preventive measures and treatment strategies.