Helicobacter pylori promotes gastric cancer progression through the GATA3-AS1/miR-30c-5p/CTHRC1 axis

Gastric cancer (GC) remains a major global health burden, often diagnosed at advanced stages with poor prognosis. Helicobacter pylori (H. pylori) infection promotes GC development through inflammation and altered signaling. Collagen triple helix repeat containing 1 (CTHRC1), a secreted ECM protein, is upregulated in several cancers and may be involved in H. pylori-related gastric tumorigenesis, though the mechanism is unclear.

H. pylori -GC cell co-culture models were used to assess CTHRC1 expression. Western blot, qRT-PCR, and immunohistochemistry evaluated expression levels in GC tissues. Bioinformatics and dual-luciferase assays explored the regulatory roles of lncRNA GATA3-AS1 and miR-30c-5p. GC cell proliferation, migration, and invasion were assessed via EdU, colony formation, wound healing, and transwell assays. H. pylori-infected mouse models were used to validate findings in vivo.

CTHRC1 was highly expressed in GC and further upregulated upon H. pylori infection. GATA3-AS1 positively regulated CTHRC1 by sponging miR-30c-5p. Inhibition of miR-30c-5p elevated CTHRC1 expression, promoting malignant GC phenotypes through activation of oncogenic pathways. H. pylori-infected mice showed decreased miR-30c-5p and increased CTHRC1 expression, supporting its role in GC progression.

H. pylori infection promotes GC progression by modulating the GATA3-AS1/miR-30c-5p/CTHRC1 axis. CTHRC1 may serve as a potential target for treating H. pylori-related gastric cancer.