Skip to main content
Top
Published in: BMC Cancer 1/2024

Open Access 01-12-2024 | Acute Myeloid Leukemia | Research

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

Authors: Miaomiao Liu, Bingxin Yu, Yong Tian, Fan Li

Published in: BMC Cancer | Issue 1/2024

Login to get access

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.
Appendix
Available only for authorised users
Literature
2.
go back to reference Wang XN, Studzinski GP. Activation of extracellular signal-regulated kinases (ERKs) defines the first phase of 1,25-dihydroxyvitamin D-3-induced differentiation of HL60 cells. J Cell Biochem. 2001;80:471–82. https://doi.org/10.1002/1097-4644(20010315)80:4<471::Aid-jcb1001>3.0.Co;2-j. Wang XN, Studzinski GP. Activation of extracellular signal-regulated kinases (ERKs) defines the first phase of 1,25-dihydroxyvitamin D-3-induced differentiation of HL60 cells. J Cell Biochem. 2001;80:471–82. https://​doi.​org/​10.​1002/​1097-4644(20010315)80:4<471::Aid-jcb1001>3.0.Co;2-j.
22.
go back to reference Yang MH, Zhao L, Wang L, Wen OY, Hu SS, Li WL, Ai ML, Wang YQ, Han Y, Li TT, Ding YQ, Wang S. Nuclear lncRNA HOXD-AS1 suppresses colorectal carcinoma growth and Metastasis via inhibiting HOXD3-induced integrin 3 transcriptional activating and MAPK/AKT signalling. Mol Cancer. 2019;18. https://doi.org/10.1186/s12943-019-0955-9. Yang MH, Zhao L, Wang L, Wen OY, Hu SS, Li WL, Ai ML, Wang YQ, Han Y, Li TT, Ding YQ, Wang S. Nuclear lncRNA HOXD-AS1 suppresses colorectal carcinoma growth and Metastasis via inhibiting HOXD3-induced integrin 3 transcriptional activating and MAPK/AKT signalling. Mol Cancer. 2019;18. https://​doi.​org/​10.​1186/​s12943-019-0955-9.
28.
go back to reference Yoshida M, Kobune M, Miura S, Ibata S, Iyama S, Sato T, Murase K, Takada K, Ono K, Hashimoto A, Tatekoshi A, Kamihara Y, Sugama Y, Kikuchi S, Ikeda H, Horiguchi H, Kawano Y, Miyanishi K, Kuroda H, Maeda M, Kato J. Extracellular vesicle microRNAs from acute myeloid leukemia are involved in the regulation of adherence junction in bone marrow microenvironment. Blood. 2016;128. https://doi.org/10.1182/blood.V128.22.2863.2863. Yoshida M, Kobune M, Miura S, Ibata S, Iyama S, Sato T, Murase K, Takada K, Ono K, Hashimoto A, Tatekoshi A, Kamihara Y, Sugama Y, Kikuchi S, Ikeda H, Horiguchi H, Kawano Y, Miyanishi K, Kuroda H, Maeda M, Kato J. Extracellular vesicle microRNAs from acute myeloid leukemia are involved in the regulation of adherence junction in bone marrow microenvironment. Blood. 2016;128. https://​doi.​org/​10.​1182/​blood.​V128.​22.​2863.​2863.
31.
go back to reference Abdi S, Zamanian Azodi M, Rezaei-Tavirani M, Razzaghi M, Heidari MH, Akbarzadeh Baghban A. Differentiation of H. Pylori-negative and positive gastric cancer via regulatory network analysis. Gastroenterol Hepatol Bed Bench. 2020;13:161–7.PubMedPubMedCentral Abdi S, Zamanian Azodi M, Rezaei-Tavirani M, Razzaghi M, Heidari MH, Akbarzadeh Baghban A. Differentiation of H. Pylori-negative and positive gastric cancer via regulatory network analysis. Gastroenterol Hepatol Bed Bench. 2020;13:161–7.PubMedPubMedCentral
35.
go back to reference Nadarajan G, Doyle S. Realistic cross-domain microscopy via conditional generative adversarial networks: converting immunofluorescence to hematoxylin and Eosin, SPIE Conference on medical imaging - digital pathology, Houston, TX. 2020. Nadarajan G, Doyle S. Realistic cross-domain microscopy via conditional generative adversarial networks: converting immunofluorescence to hematoxylin and Eosin, SPIE Conference on medical imaging - digital pathology, Houston, TX. 2020.
36.
go back to reference Alspach E, Stewart SA. RNA-binding Protein Immunoprecipitation (RIP) to examine AUF1 binding to Senescence-Associated Secretory Phenotype (SASP) factor mRNA. Bio Protoc. 2015;5(10):e1481.CrossRefPubMed Alspach E, Stewart SA. RNA-binding Protein Immunoprecipitation (RIP) to examine AUF1 binding to Senescence-Associated Secretory Phenotype (SASP) factor mRNA. Bio Protoc. 2015;5(10):e1481.CrossRefPubMed
37.
go back to reference Dang WQ, Tang H, Cao H, Wang L, Chen TM. Construction of lentivirus-mediated short hairpin RNA targeting human STAT3 gene. Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi. 2012;28:1204–7.PubMed Dang WQ, Tang H, Cao H, Wang L, Chen TM. Construction of lentivirus-mediated short hairpin RNA targeting human STAT3 gene. Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi. 2012;28:1204–7.PubMed
41.
go back to reference Zhang Z, Li SY, Zhang LB. LncRNA RGMB-AS1 is activated by E2F1 and promotes cell proliferation and invasion in papillary thyroid carcinoma. Eur Rev Med Pharmacol Sci. 2018;22:1979–86.PubMed Zhang Z, Li SY, Zhang LB. LncRNA RGMB-AS1 is activated by E2F1 and promotes cell proliferation and invasion in papillary thyroid carcinoma. Eur Rev Med Pharmacol Sci. 2018;22:1979–86.PubMed
50.
go back to reference Liu SS, Zhang JF, Yin LY, Wang XX, Zheng Y, Zhang YJ, Gu JY, Yang L, Yang J, Zheng P, Jiang Y, Shuai L, Cai XW, Wang HZ. The lncRNA RUNX1-IT1 regulates C-FOS transcription by interacting with RUNX1 in the process of pancreatic cancer proliferation, migration and invasion. Cell Death Dis. 2020;11. https://doi.org/10.1038/s41419-020-2617-7. Liu SS, Zhang JF, Yin LY, Wang XX, Zheng Y, Zhang YJ, Gu JY, Yang L, Yang J, Zheng P, Jiang Y, Shuai L, Cai XW, Wang HZ. The lncRNA RUNX1-IT1 regulates C-FOS transcription by interacting with RUNX1 in the process of pancreatic cancer proliferation, migration and invasion. Cell Death Dis. 2020;11. https://​doi.​org/​10.​1038/​s41419-020-2617-7.
Metadata
Title
Regulatory function and mechanism research for m6A modification WTAP via SUCLG2-AS1- miR-17-5p-JAK1 axis in AML
Authors
Miaomiao Liu
Bingxin Yu
Yong Tian
Fan Li
Publication date
01-12-2024
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2024
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/s12885-023-11687-4

Other articles of this Issue 1/2024

BMC Cancer 1/2024 Go to the issue
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine