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Research Paper|Volume 16, Issue 2|pp 1496—1515

The miR-146b-3p/TNFAIP2 axis regulates cell differentiation in acute myeloid leukaemia

Gaochen Lan1, Xiaolong Wu2, Aiyue Zhao1, Jinjian Lan3, Qiusheng Guo4, Bolin Wang5, Fenglin Shen3, Xiaoling Yu5, Yanna Zhao5, Ruilan Gao5, Tianwen Xu1
  • 1Department of Oncology, The Second Affiliated Hospital of Fujian Medical University, Quanzhou, China
  • 2College of Life Science, Zhejiang Chinese Medical University, Hangzhou, China
  • 3The First Clinical College, Zhejiang Chinese Medical University, Hangzhou, China
  • 4Department of Oncology, Affiliated Jinhua Hospital, Zhejiang University School of Medicine, Jinhua, China
  • 5Institute of Hematology, The First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, China
* Equal contribution
Received: June 29, 2023Accepted: December 1, 2023Published: January 24, 2024
https://doi.org/10.18632/aging.205441

Copyright: © 2024 Lan et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

Our purpose is to verify that miR-146b-3p targets the downstream transcript TNFAIP2 in order to reveal the machinery underlying the miR-146b-3p/TNFAIP2 axis regulating acute myeloid leukaemia (AML) differentiation. Bioinformatics analyses were performed using multiple databases and R packages. The CD11b+ and CD14+ cell frequencies were detected using flow cytometry and immunofluorescence staining. The TNFAIP2 protein expression was evaluated using western blotting, immunocytochemistry and immunofluorescence staining. The qRT-PCR was conducted to detect the expression of TNFAIP2 and miR-146b-3p. TNFAIP2 and its correlated genes were enriched in multiple cell differentiation pathways. TNFAIP2 was upregulated upon leukaemic cell differentiation. miR-146b-3p directly targeted TNFAIP2, resulting in a decrease in TNFAIP2 expression. Forced expression of TNFAIP2 or knockdown of miR-146b-3p significantly induced the differentiation of MOLM-13 cells. In this study, we demonstrated that TNFAIP2 is a critical driver in inducing differentiation and that the miR-146b-3p/TNFAIP2 axis involves in regulating cell differentiation in AML.