Abstract
Circular RNAs (circRNAs) are a type of non-coding RNA molecule whose functional processes in carcinogenesis and progression are not fully known. Recent studies suggest that circRNAs can act as functional RNAs involved in the progression of various tumors. This study aims to investigate the role of hsa_circ_0085465 in the proliferation, migration, and invasion processes of gastric cancer cells. By establishing models of Helicobacter pylori (H. pylori)-infected normal gastric epithelial cells and gastric cancer cells, we conducted whole transcriptome sequencing and bioinformatics analysis, which led to the identification of a significantly upregulated circular RNA molecule, hsa_circ_0085465. Subsequently, we investigated the function of hsa_circ_0085465 in gastric cancer through in vitro functional experiments, including scratch wound healing assays and transwell assays, as well as in vivo animal experiments. Then, the downstream target miRNA of hsa_circ_0085465 were identified using sequencing and bioinformatics analysis, and the binding between hsa_circ_0085465 and the target gene miR-33b-3p was validated using dual-luciferase reporter gene assays and fluorescence in situ hybridization (FISH). Finally, we explored the interaction between hsa_circ_0085465 and miR-33b-3p through in vitro functional analyses. In a gastric cell model infected with H. pylori, the expression level of hsa_circ_0085465 was significantly upregulated. In vitro experiments demonstrated that hsa_circ_0085465 promotes the proliferation, migration, and invasion of gastric cancer cells, while in vivo subcutaneous tumor model further confirmed that hsa_circ_0085465 markedly accelerates tumor growth. Subsequent analyses identified miR-33b-3p as a downstream target of hsa_circ_0085465, and miR-33b-3p was found to suppress the proliferation, migration, and invasion of gastric cancer cells. Rescue experiments further demonstrated that miR-33b-3p can partially reverse the oncogenic effects of hsa_circ_0085465 in gastric cancer. H. pylori induced the upregulation of hsa_circ_0085465 in gastric cells, and hsa_circ_0085465 functions as a molecular sponge for miR-33b-3p, thereby promoting the proliferation, migration, and invasion of gastric cancer cells.
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Acknowledgements
I would like to express my gratitude to the fundings support of this project, as well as my gratitude to my advisors, Zhang Zhen and Prof. Guo Le , and to my team members, Zhang Furui, Chen Jiale, and Ni Linhan, for their assistance and companionship. We also thank the Medical Sci-Tech Research Center of Ningxia Medical University (Medical Science Research Institution of Ningxia Hui Autonomous Region) for valuable assistance with our experiments.
Funding
The author(s) declared financial support was received for the research and/or publication of this article. This study was financially supported by the National Natural Science Foundation of China (82360711), Natural Science Foundation of Ningxia (2025AAC030692), Open subject of Ningxia Key Laboratory of Clinical Pathogenic Microbiology (MKLG-2024-02), Ningxia Youth Top Talent Training Project, Leading Talent Development Program in Science and Technology of Ningxia (2025GKLRLX14), Research Project of the Health System of Ningxia Hui Autonomous Region (2023-NWKYP-045) and Ningxia Key Research and Development Program Project (2026BEG02024).
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Animal Experiment Ethics Committee of Ningxia Medical University approved the animal study. The study was conducted in accordance with the local legislation and institutional requirements.
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Wu, J., Liu, H., Zhang, F. et al. H. pylori-induced hsa_circ_0085465 promotes gastric cancer cell proliferation, migration, and invasion by sponging miR-33b-3p. Sci Rep (2026). https://doi.org/10.1038/s41598-026-55204-6
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DOI: https://doi.org/10.1038/s41598-026-55204-6
