多发性骨髓瘤（MM）是一种致命的浆细胞恶性肿瘤，其发病机制难以捉摸。 N6-甲基腺苷 (m6A) 在血液恶性肿瘤中发挥着重要作用。甲基转移酶的最大组成部分 KIAA1429 的功能尚不清楚。本研究深入探讨KIAA1429在MM中的作用机制，希望为MM治疗提供新的靶点。采集了55名MM患者和15名对照者的骨髓样本。检测KIAA1429、YTHDF1、FOXM1 mRNA水平并分析其相关性。证实了细胞活力、增殖、细胞周期和凋亡。评估了糖酵解增强基因（HK2、ENO1 和 LDHA）、乳酸生成和葡萄糖摄取。检测了 FOXM1 mRNA 与 YTHDF1 之间的相互作用、m6A 修饰的 FOXM1 水平以及 FOXM1 稳定性。建立移植肿瘤模型以证实 KIAA1429 的机制。KIAA1429 在 MM 患者和 MM 细胞中处于高水平，并与不良预后相关。 KIAA1429 敲低可抑制 MM 细胞活力和增殖，阻止 G0/G1 期并增加细胞凋亡。 MM 患者浆细胞中的 KIAA1429 mRNA 与糖酵解增强基因呈正相关。敲除 KIAA1429 后，糖酵解增强基因、葡萄糖摄取和乳酸生成的水平受到抑制，同时 FOXM1 水平和稳定性也降低。 YTHDF1 识别 KIAA1429 甲基化的 FOXM1 mRNA 并提高 FOXM1 稳定性。 YTHDF1 的敲低抑制了 MM 细胞中的有氧糖酵解和恶性行为，而 FOXM1 过表达则使这种行为无效。在动物实验中，KIAA1429 敲低也抑制肿瘤生长。KIAA1429 敲低通过 YTHDF1 介导的 m6A 修饰降低 FOXM1 表达，从而抑制 MM 有氧糖酵解和肿瘤发生。© 2024。作者。

Multiple myeloma (MM) is a deadly plasma cell malignancy with elusive pathogenesis. N6-methyladenosine (m6A) is critically engaged in hematological malignancies. The function of KIAA1429, the largest component of methyltransferases, is unknown. This study delved into the mechanism of KIAA1429 in MM, hoping to offer novel targets for MM therapy.Bone marrow samples were attained from 55 MM patients and 15 controls. KIAA1429, YTHDF1, and FOXM1 mRNA levels were detected and their correlation was analyzed. Cell viability, proliferation, cell cycle, and apoptosis were testified. Glycolysis-enhancing genes (HK2, ENO1, and LDHA), lactate production, and glucose uptake were evaluated. The interaction between FOXM1 mRNA and YTHDF1, m6A-modified FOXM1 level, and FOXM1 stability were assayed. A transplantation tumor model was built to confirm the mechanism of KIAA1429.KIAA1429 was at high levels in MM patients and MM cells and linked to poor prognoses. KIAA1429 knockdown restrained MM cell viability, and proliferation, arrested G0/G1 phase, and increased apoptosis. KIAA1429 mRNA in plasma cells from MM patients was positively linked with to glycolysis-enhancing genes. The levels of glycolysis-enhancing genes, glucose uptake, and lactate production were repressed after KIAA1429 knockdown, along with reduced FOXM1 levels and stability. YTHDF1 recognized KIAA1429-methylated FOXM1 mRNA and raised FOXM1 stability. Knockdown of YTHDF1 curbed aerobic glycolysis and malignant behaviors in MM cells, which was nullified by FOXM1 overexpression. KIAA1429 knockdown also inhibited tumor growth in animal experiments.KIAA1429 knockdown reduces FOXM1 expression through YTHDF1-mediated m6A modification, thus inhibiting MM aerobic glycolysis and tumorigenesis.© 2024. The Author(s).