Copyright
©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.
GATA binding protein 2 mediated ankyrin repeat domain containing 26 high expression in myeloid-derived cell lines
Yang-Zhou Jiang, Lan-Yue Hu, Mao-Shan Chen, Xiao-Jie Wang, Cheng-Ning Tan, Pei-Pei Xue, Teng Yu, Xiao-Yan He, Li-Xin Xiang, Yan-Ni Xiao, Xiao-Liang Li, Qian Ran, Zhong-Jun Li, Li Chen
Yang-Zhou Jiang, Lan-Yue Hu, Mao-Shan Chen, Xiao-Jie Wang, Cheng-Ning Tan, Pei-Pei Xue, Teng Yu, Xiao-Yan He, Li-Xin Xiang, Yan-Ni Xiao, Xiao-Liang Li, Qian Ran, Zhong-Jun Li, Li Chen, Laboratory of Radiation Biology, Department of Blood Transfusion, Laboratory Medicine Center, The Second Affiliated Hospital, Third Military Medical University, Chongqing 400037, China
Yang-Zhou Jiang, Lan-Yue Hu, Mao-Shan Chen, Xiao-Jie Wang, Cheng-Ning Tan, Pei-Pei Xue, Teng Yu, Xiao-Yan He, Li-Xin Xiang, Yan-Ni Xiao, Xiao-Liang Li, Qian Ran, Zhong-Jun Li, Li Chen, Hematopoietic Acute Radiation Syndrome Medical and Pharmaceutical Basic Research Innovation Center, Ministry of Education of the People’s Republic of China, Chongqing 400037, China
Co-first authors: Yang-Zhou Jiang and Lan-Yue Hu.
Co-corresponding authors: Li Chen and Zhong-Jun Li.
Author contributions: Chen L and Li ZJ collaboratively established the research framework, methodology, and provided comprehensive strategic guidance; Ran Q ensured seamless coordination throughout the entire research process; Jiang YZ and Hu LY as co-first authors, undertook the core experimental work; Chen MS, Yu T, He XY, and Li XL provided indispensable support for the experiment’s execution; Chen MS, Xiang LX, and Xiao YN carried out the meticulous data collection and analysis; Xue PP, Wang XJ, and Tan CN delved into the data interpretation; Jiang YZ and Hu LY crafted the manuscript skillfully, reflecting their academic proficiency and expressive ability; and all authors collectively reviewed and approved the final outcome of this study.
Supported by General Program of National Natural Science Foundation of China, No. 81770197; Scientific and Technological Research Major Program of Chongqing Municipal Education Commission, No. KJZD-M202312802; Chongqing Natural Science Foundation of China, No. CSTB2022NSCQ-MSX0190, No. CSTB2022NSCQ-MSX0176, and No. cstc2020jcyj-msxmX0051; and Xinqiao Young Postdoc Talent Incubation Program, No. 2022YQB098.
Institutional review board statement: The study was reviewed and approved by the Medical Ethics Committee of Second Affiliated Hospital of Army Medical University (Approval No. 2020-074-01).
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
Data sharing statement: No additional data are available.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:
https://creativecommons.org/Licenses/by-nc/4.0/ Corresponding author: Li Chen, MD, PhD, Professor, Laboratory of Radiation Biology, Department of Blood Transfusion, Laboratory Medicine Center, The Second Affiliated Hospital, Third Military Medical University, Xinqiao Street, Chongqing 400037, China.
chenli200401@163.com
Received: December 26, 2023
Revised: March 12, 2024
Accepted: April 12, 2024
Published online: May 26, 2024
Processing time: 150 Days and 4.5 Hours
BACKGROUND
Thrombocytopenia 2, an autosomal dominant inherited disease characterized by moderate thrombocytopenia, predisposition to myeloid malignancies and normal platelet size and function, can be caused by 5’-untranslated region (UTR) point mutations in ankyrin repeat domain containing 26 (ANKRD26). Runt related transcription factor 1 (RUNX1) and friend leukemia integration 1 (FLI1) have been identified as negative regulators of ANKRD26. However, the positive regulators of ANKRD26 are still unknown.
AIM
To prove the positive regulatory effect of GATA binding protein 2 (GATA2) on ANKRD26 transcription.
METHODS
Human induced pluripotent stem cells derived from bone marrow (hiPSC-BM) and urothelium (hiPSC-U) were used to examine the ANKRD26 expression pattern in the early stage of differentiation. Then, transcriptome sequencing of these iPSCs and three public transcription factor (TF) databases (Cistrome DB, animal TFDB and ENCODE) were used to identify potential TF candidates for ANKRD26. Furthermore, overexpression and dual-luciferase reporter experiments were used to verify the regulatory effect of the candidate TFs on ANKRD26. Moreover, using the GENT2 platform, we analyzed the relationship between ANKRD26 expression and overall survival in cancer patients.
RESULTS
In hiPSC-BMs and hiPSC-Us, we found that the transcription levels of ANKRD26 varied in the absence of RUNX1 and FLI1. We sequenced hiPSC-BM and hiPSC-U and identified 68 candidate TFs for ANKRD26. Together with three public TF databases, we found that GATA2 was the only candidate gene that could positively regulate ANKRD26. Using dual-luciferase reporter experiments, we showed that GATA2 directly binds to the 5’-UTR of ANKRD26 and promotes its transcription. There are two identified binding sites of GATA2 that are located 2 kb upstream of the TSS of ANKRD26. In addition, we discovered that high ANKRD26 expression is always related to a more favorable prognosis in breast and lung cancer patients.
CONCLUSION
We first discovered that the transcription factor GATA2 plays a positive role in ANKRD26 transcription and identified its precise binding sites at the promoter region, and we revealed the importance of ANKRD26 in many tissue-derived cancers.
Core Tip: The 5’-untranslated region mutation of ankyrin repeat domain containing 26 (ANKRD26) plays an important role in the pathology of thrombocytopenia 2 (THC2). Considering the predisposition of THC2 patients to myeloid malignancies, further revealing the molecular mechanism of ANKRD26 transcription is warranted. Although Runt related transcription factor 1 and friend leukemia integration 1 have been shown to negatively regulate ANKRD26 expression, no known positive regulators have been reported. Here, we first revealed that GATA binding protein 2 mediates high ANKRD26 expression by binding to its promoter region. We discovered that high ANKRD26 expression was always associated with favorable overall survival. Our study provides insights into the regulatory network of ANKRD26 and the pathological process of THC2.
