Helicobacter pylori infection accelerates gastric cancer development by acting on the miR-146a-5p/FHL1 axis

Autor: Feng Ju, Jin-bang Peng, Ying-ying Zhang, Lu Zhou, Shang-zhi Yao, Dong Wang, Yan-hong Zhu, Jun Liu, Lei Li, Jun-feng Bao, Shuan Tang
Rok vydání: 2023
DOI: 10.21203/rs.3.rs-2676039/v1
Popis: Background: Gastric cancer (GC) is a common malignancy globally. The main risk factor for GC is Helicobacter pylori (H. pylori) infection. miR-146a-5p regulates vital functions in numerous human cancers. However, miR-146a-5p's impacts on H. pylori-associated GC have not been fully elucidated. Objective This study aim to explore the role of miR-146a-5p in H. pylori-associated GC and identify the downstream pathway through which it facilitates the progression of GC. Methods: miRNAs relevant to H. pylori and GC were obtained from the GeneCards, miRTarBase, and ENCORI databases. Its expressions in H. pylori-induced GC were examined using quantitative real-time PCR. Cell Counting Kit-8, clone formation analysis, scratch wound healing analysis, Transwell analysis, flow cytometry, and western blot assays were performed to assess the role of miR-146a-5p in H. pylori-associated GC. Besides, a dual-luciferase reporter assay was carried out to assess the mechanism of miR-146a-5p in GC. Results: miR-146a-5p was highly expressed in H. pylori-infected GC cell lines. Functionally, H. pylori infection induced the proliferation, metastasis, and migratory abilities of GC cell lines via increasing the expression level of miR-146a-5p. Mechanistically, miR-146a-5p targets the "Four and a Half LIM Domains 1 (FHL1) gene. Subsequent assays further authenticated that H. pylori increased GC cells' proliferation by enhancing the expression of miR-146a-5p and decreasing the expression of FHL1. Conclusion:miR-146a-5p could be the future diagnostic biomarker and potential therapeutic target for H. pylori-induced GC as it aggravates GC development via upregulation of miR-146a-5p.
Databáze: OpenAIRE