Department of Radiation Oncology, The First Affiliated Hospital of Xi'an Jiaotong University, 277 West Yanta Road, Xi'an, Shaanxi, 710061, People's Republic of China.
Department of Thoracic Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, 277 West Yanta Road, Xi'an, Shaanxi, China.
Mol Biotechnol. 2024 Sep;66(9):2415-2425. doi: 10.1007/s12033-023-00877-x. Epub 2023 Sep 21.
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.
KLHL5 是 kelch 重复蛋白家族的成员，参与了多种癌症的进展的启动。然而，其在胃癌中的具体作用尚未明确说明。在这种情况下，我们旨在研究 KLHL5 在胃癌中的生物学作用和机制。qRT-PCR 和 Western blot 用于研究 KLHL5 和 EMT 生物标志物的表达。伤口愈合试验、CCK-8 和 Transwell 试验用于研究 KLHL5 的生物学功能。我们发现 KLHL5 在体内和体外均在胃癌中高度表达；此外，其高表达导致总生存期缩短。统计分析表明，KLHL5 与 M 期有关。至于分子实验，我们发现 KLHL5 敲低显著降低了胃癌细胞系 MKN45 和 SGC-7901 的增殖、迁移和侵袭能力。此外，我们发现 miR-181-5p 通过 METTL3 靶向 KLHL5 来调节 m6A 水平。此外，KLHL5 敲低可显著降低小鼠的肺转移率。总之，我们发现 miR-181-5p/KLHL5 通过调节 METTL3 激活 m6A 过程，可促进胃癌的增殖、迁移和侵袭。
