Helicobacter pylori contributes to GC progression, possibly via the MSTRG.10627.1/miR-142-5p/ADAMTS5 pathway

Area of Science:

• Oncology
• Molecular Biology
• Microbiology

Background:

• Helicobacter pylori (H. pylori) is a class I carcinogen linked to gastric cancer (GC).
• The precise molecular mechanisms by which H. pylori induces GC remain incompletely understood.
• This study investigates the role of the MSTRG.10627.1/miR-142-5p/ADAMTS5 pathway in H. pylori-mediated GC pathogenesis.

Purpose of the Study:

• To identify and characterize a novel regulatory pathway involved in H. pylori-induced gastric cancer.
• To elucidate the function of the MSTRG.10627.1/miR-142-5p/ADAMTS5 axis in GC cell behavior.
• To validate the role of ADAMTS5 in GC progression and metastasis in vivo.

Main Methods:

• RNA sequencing and bioinformatics analysis to screen lncRNA-miRNA-mRNA regulatory pathways.
• Dual luciferase reporter assays to confirm interactions between pathway components.
• In vitro assays (clonogenic formation, cell migration) and western blotting to assess ADAMTS5 function and protein expression.
• In vivo studies using nude mice (subcutaneous and tail vein injections) to evaluate tumor growth and metastasis.

Main Results:

• A significant regulatory axis, MSTRG.10627.1-miR-142-5p-ADAMTS5, was identified and validated.
• H. pylori down-regulates ADAMTS5 expression in GC cells (p < 0.05).
• Down-regulation of ADAMTS5 enhances GC cell proliferation, migration, and invasion, while its overexpression inhibits these processes (p < 0.05).
• Silencing ADAMTS5 increases PI3K and phosphorylated AKT, and decreases p53 expression, promoting tumor growth and metastasis in vivo.

Conclusions:

• H. pylori down-regulates ADAMTS5 via the MSTRG.10627.1-miR-142-5p-ADAMTS5 pathway, contributing to GC development.
• The observed changes in PI3K, p-AKT, and p53 signaling downstream of ADAMTS5 are critical for H. pylori-induced GC.
• Targeting the ADAMTS5 pathway presents a potential therapeutic strategy for H. pylori-associated gastric cancer.