KLHL5是kelch-repeat蛋白家族中的成员，参与了众多癌症的进展和发展。然而，它在胃癌中的具体作用尚未明确阐明。在这个背景下，我们旨在研究KLHL5在胃癌中的生物学作用和机制。使用qRT-PCR和western blot研究了KLHL5和EMT生物标志物的表达。使用划痕愈合实验、CCK-8实验和Transwell实验研究了KLHL5的生物功能。我们发现KLHL5在胃癌中无论在体内还是体外都高表达；此外，其高表达导致了更短的总生存期。随后的统计分析表明KLHL5与M期密切相关。至于分子实验，我们发现KLHL5沉默显著降低了胃癌细胞株MKN45和SGC-7901的增殖、迁移和侵袭能力。此外，我们还发现miR-181-5p通过靶向KLHL5来调节通过METTL3调节m6A水平。此外，KLHL5沉默能够显著降低小鼠的肺转移率。总之，我们发现miR-181-5p/KLHL5通过激活m6A过程通过调节METTL3促进了胃癌的增殖、迁移和侵袭。© 2023年。作者，独家授权给施普林格科学+商业传媒有限公司，施普林格自然出版集团的一部分。

KLHL5 was a member of kelch-repeat protein family and was involved in the initiation of progression of a plethora of cancers. However, its specific role in gastric cancer was not explicitly illustrated. In this context, we aimed to investigate the biological role and mechanisms about KLHL5 in gastric cancer. qRT-PCR and western blot were used to investigate the expression of KLHL5 and EMT biomarkers. Wound healing assay, CCK-8, and Transwell assay were used to investigate the biological function of KLHL5. We found that KLHL5 was highly expressed in gastric cancer both in vivo and in vitro; besides, its high expression led to a shorter overall survival. Following statistical analysis showed that KLHL5 was associated with M stage. As for molecular experiments, we found that KLHL5 knockdown significantly reduced the proliferation, migration, and invasion ability of gastric cancer cell line MKN45 and SGC-7901. Furthermore, we found that miR-181-5p targeted KLHL5 to regulate m6A level through METTL3. In addition, KLHL5 knockdown could significantly reduce the lung metastasis rate in mice. In conclusion, we found that miR-181-5p/KLHL5 could promote the proliferation, migration, and invasion of gastric cancer by activating m6A process through regulating METTL3.© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.