RNA N6-甲基腺苷（m6A）修饰影响胃肠道间质瘤（GISTs）的发展，但其详细的分子机制尚未完全研究。在这里，我们发现微RNA-675在GISTs的癌组织和细胞中异常升高，与相应的正常对照组织相比，而高表达微RNA-675的GISTs患者预后更差。额外的实验证实，静默微RNA-675会阻碍细胞分裂、迁移和体内外肿瘤发生，而在GISTs细胞中引发凋亡性细胞死亡。此外，微RNA-675消融增加了肌凝集酶磷酸酶靶向蛋白1（MYPT1）的表达水平，从而失活肿瘤起始RhoA/NF2/YAP1信号通路，而MYPT1的下调恢复了微RNA-675静默的GISTs细胞的恶性表型。另外，我们证明了METTL3介导的m6A修饰对于维持微RNA-675的稳定是必需的，而METTL3的沉默通过调控微RNA-675/MYPT1轴抑制了GISTs细胞的肿瘤发生。总之，METTL3/m6A/微RNA-675/MYPT1轴可用作GISTs的诊断和治疗的新生物标志物。版权所有 © 2023. Elsevier Inc.出版。

RNA N6-methyladenosine (m6A) modifications influence gastrointestinal stromal tumors (GISTs) development, but the detailed molecular mechanisms have not been fully studied. Here, microRNA-675 was found to be aberrantly elevated in cancerous tissues and cells of GISTs, compared to the corresponding normal counterparts, and GISTs patients with high-expressed microRNA-675 have worse outcomes. Additional experiments confirmed that silencing of microRNA-675 hindered cell division, mobility and tumorigenesis in vitro and in vivo, whereas triggered apoptotic cell death in GISTs cells. Furthermore, microRNA-675-ablation increased the expression levels of myosin phosphatase targeting protein 1 (MYPT1) to inactivate the tumor-initiating RhoA/NF2/YAP1 signal pathway, and downregulation of MYPT1 recovered the malignant phenotypes in microRNA-675-silenced GISTs cells. In addition, we evidenced that METTL3-mediated m6A modifications were essential for sustaining the stability of microRNA-675, and silencing of METTL3 restrained tumorigenesis of GISTs cells by regulating the microRNA-675/MYPT1 axis. To summarize, theMETTL3/m6A/microRNA-675/MYPT1 axis could be used as novel biomarkers for the diagnosis and treatment of GISTs.Copyright © 2023. Published by Elsevier Inc.