通过 SUCLG2-AS1- miR-17-5p-JAK1 轴调控 WTAP 上 m6A 修饰在 AML 中的作用及机制研究。

Regulatory function and mechanism research for m6A modification WTAP via SUCLG2-AS1- miR-17-5p-JAK1 axis in AML.

机构信息

Department of Pathogenobiology, The Key Laboratory of Zoonosis, Chinese Ministry of Education, College of Basic Medicine, Jilin University, No.126 Xinmin Street, Changchun, Jilin, 130021, P.R. China.

Department of Ultrasonography, The Third Hospital of Jilin University, Changchun, Jilin, 130033, P.R. China.

出版信息

BMC Cancer. 2024 Jan 17;24(1):98. doi: 10.1186/s12885-023-11687-4.

DOI:10.1186/s12885-023-11687-4

PMID:38233760

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10795285/

Abstract

Acute myeloid leukemia (AML), characterized by the abnormal accumulation of immature marrow cells in the bone marrow, is a malignant tumor of the blood system. Currently, the pathogenesis of AML is not yet clear. Therefore, this study aims to explore the mechanisms underlying the development of AML. Firstly, we identified a competing endogenous RNA (ceRNA) SUCLG2-AS1-miR-17-5p-JAK1 axis through bioinformatics analysis. Overexpression of SUCLG2-AS1 inhibits proliferation, migration and invasion and promotes apoptosis of AML cells. Secondly, luciferase reporter assay and RIP assay validated that SUCLG2-AS1 functioned as ceRNA for sponging miR-17-5p, further leading to JAK1 underexpression. Additionally, the results of MeRIP-qPCR and m6A RNA methylation quantification indicted that SUCLG2-AS1(lncRNA) had higher levels of m6A RNA methylation compared with controls, and SUCLG2-AS1 is regulated by m6A modification of WTAP in AML cells. WTAP, one of the main regulatory components of m6A methyltransferase complexes, proved to be highly expressed in AML and elevated WTAP is associated with poor prognosis of AML patients. Taken together, the WTAP-SUCLG2-AS1-miR-17-5p-JAK1 axis played essential roles in the process of AML development, which provided a novel therapeutic target for AML.

摘要

急性髓细胞白血病（AML），其特征是骨髓中不成熟的骨髓细胞异常积聚，是一种血液系统的恶性肿瘤。目前，AML 的发病机制尚不清楚。因此，本研究旨在探索 AML 发生发展的机制。首先，我们通过生物信息学分析鉴定了一个竞争性内源性 RNA（ceRNA）SUCLG2-AS1-miR-17-5p-JAK1 轴。SUCLG2-AS1 的过表达抑制 AML 细胞的增殖、迁移和侵袭，促进细胞凋亡。其次，荧光素酶报告基因检测和 RIP 实验验证了 SUCLG2-AS1 作为 miR-17-5p 的 ceRNA 发挥作用，进而导致 JAK1 表达下调。此外，MeRIP-qPCR 和 m6A RNA 甲基化定量分析的结果表明，与对照组相比，SUCLG2-AS1（lncRNA）的 m6A RNA 甲基化水平更高，并且在 AML 细胞中，SUCLG2-AS1 受 WTAP 的 m6A 修饰调控。WTAP 是 m6A 甲基转移酶复合物的主要调节成分之一，在 AML 中高表达，且升高的 WTAP 与 AML 患者的不良预后相关。综上所述，WTAP-SUCLG2-AS1-miR-17-5p-JAK1 轴在 AML 发展过程中发挥着重要作用，为 AML 的治疗提供了新的靶点。