Pseudogene BNIP3P1 Regulates H. pylori–Induced Apoptosis in Gastric Mucosal by Acting on the miR-411-5p/BNIP3 Axis

Abstract

Helicobacter pylori (H. pylori) is one of the major causes of gastric mucosal damage, and infection with H. pylori induces an immune response with gastric mucosal cells, which reduces gastric mucosal damage. The pseudogene BNIP3P1, sharing a remarkable 95.92% similarity with its well-characterized counterpart BNIP3, has largely remained unexplored. To elucidate the role of BNIP3P1 in gastric mucosal damage induced by H. pylori infection, we meticulously constructed both in vivo and in vitro models. Gene chip sequencing, dual-luciferase assays, and cellular phenotyping were detected. We uncovered a compelling positive correlation between the duration of H. pylori infection and BNIP3 overexpression at both the mRNA and protein levels. Intriguingly, overexpression of BNIP3 was found to effectively impede the proliferation and migration of human gastric epithelial cells (GES-1). Furthermore, we identified miR-411-5p as a direct regulator of BNIP3, targeting its 3 ^′UTR region and suppressing its expression during H. pylori infection. Notably, BNIP3P1- 3^′UTR was observed to competitively bind miR-411-5p, leading to the upregulation of BNIP3 expression. Furthermore, overexpression of BNIP3P1 was associated with a marked decrease in GES-1 cell proliferation and a concomitant acceleration of apoptosis. Our findings suggest that BNIP3P1 functions as a competing endogenous RNA (ceRNA) within the BNIP3/miR-411-5p axis during H. pylori infection, which ultimately hinders cell proliferation and promotes apoptosis in GES-1 cells. This study sheds light on the intricate mechanisms underlying H. pylori infection of GES-1 cells.