MiR-216a-5p inhibits proliferation, migration, and enhances oxaliplatin sensitivity by targeting ZBTB2 in gastric cancer cells.

[BACKGROUND] Although miR-216a-5p is linked to tumour progression and chemoresistance, its mechanistic contributions to gastric cancer (GC) remain undefined. This study sought to clarify the role of miR-216a-5p in GC progression and its impact on oxaliplatin (OXA) resistance.

[METHODS] MiR-216a-5p expression in GC specimens and cell lines was assessed by quantitative real-time polymerase chain reaction (qRT-PCR). Bioinformatics and dual-luciferase reporter assays were employed to identify and, subsequently, validate ZBTB2 as a direct target of miR-216a-5p, which was further confirmed through RNA immunoprecipitation, Western blot, and qRT-PCR analyses. In vitro functional assays, including proliferation, migration, and drug sensitivity assays, assessed the effects of miR-216a-5p and ZBTB2 on GC cells. Rescue experiments further elucidated the miR-216a-5p/ZBTB2 regulatory axis. Additionally, in vivo experiments substantiated these findings.

[RESULTS] Quantitative analyses revealed substantial downregulation of miR-216a-5p in both clinical GC samples and cellular models relative to matched non-neoplastic mucosal tissues and normal epithelial controls. Functional assays demonstrated that miR-216a-5p inhibited GC cell proliferation and migration while enhancing their sensitivity to OXA. Mechanistically, miR-216a-5p directly targeted and downregulated ZBTB2, thereby modulating GC cell growth and chemoresistance. Rescue experiments confirmed that ZBTB2 overexpression partially reversed the effects of miR-216a-5p on GC cells. In vivo studies further supported the tumour-suppressive role of miR-216a-5p and its regulation of ZBTB2.

[CONCLUSION] This study demonstrated that miR-216a-5p suppresses GC by inhibiting cell proliferation, migration, and OXA resistance through the downregulation of ZBTB2. Our findings underscored miR-216a-5p's role as a potential molecular target for improving chemotherapy efficacy against GC.