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

Miaomiao Liu; Bingxin Yu; Yong Tian; Fan Li

doi:10.1186/s12885-023-11687-4

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

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

Authors

Miaomiao Liu¹, Bingxin Yu², Yong Tian³, Fan Li^{4

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Affiliations

¹ 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.
² Department of Ultrasonography, The Third Hospital of Jilin University, Changchun, Jilin, 130033, P.R. China.
³ Department of Human Anatomy, Chinese Ministry of Education, College of Basic Medicine, Jilin University, Changchun, Jilin, 130021, P.R. China.
⁴ 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. lifan@jlu.edu.cn.
⁵ The Key Laboratory for Bionics Engineering, Ministry of Education, Jilin University, Changchun, 130021, P.R. China. lifan@jlu.edu.cn.
⁶ Engineering Research Center for Medical Biomaterials of Jilin Province, Jilin University, Changchun, 130021, P.R. China. lifan@jlu.edu.cn.
⁷ Key Laboratory for Health Biomedical Materials of Jilin Province, Jilin University, Changchun, 130021, P.R. China. lifan@jlu.edu.cn.
⁸ State Key Laboratory of Pathogenesis, Prevention and Treatment of High Incidence Diseases in Central Asia, Urumqi, Xinjiang, 830017, P.R. China. lifan@jlu.edu.cn.

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.

Keywords: AML; JAK1; WTAP; lncRNA SUCLG2-AS1; miR-17-5p.

MeSH terms

Adenine / analogs & derivatives*
Cell Cycle Proteins
Cell Proliferation / genetics
Humans
Janus Kinase 1 / genetics
Leukemia, Myeloid, Acute* / genetics
MicroRNAs* / genetics
RNA Splicing Factors
RNA, Long Noncoding* / genetics

Substances

MicroRNAs
6-methyladenine
RNA, Long Noncoding
WTAP protein, human
RNA Splicing Factors
Cell Cycle Proteins
JAK1 protein, human
Janus Kinase 1
MIRN17 microRNA, human
Adenine

Abstract

MeSH terms

Substances

Grants and funding