DBN1‑mediated upregulation of GAB2 facilitates the migration and invasion of T‑cell acute lymphoblastic leukemia cells

Sun,Jiaxing; Huang,Xiaoxing; Zeng,Xingruo; Lei,Yufei; He,Hengjing; Wei,Zimeng; Xiao,Di; Zhang,Qiuping; Li,Xinran; Zhou,Fuling; Shao,Liang

doi:10.3892/or.2025.8982

DBN1‑mediated upregulation of GAB2 facilitates the migration and invasion of T‑cell acute lymphoblastic leukemia cells

Authors:
- Jiaxing Sun
- Xiaoxing Huang
- Xingruo Zeng
- Yufei Lei
- Hengjing He
- Zimeng Wei
- Di Xiao
- Qiuping Zhang
- Xinran Li
- Fuling Zhou
- Liang Shao
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Affiliations: Department of Hematology, Zhongnan Hospital of Wuhan University, Wuhan, Hubei 430071, P.R. China, Department of Blood Transfusion, Zhongnan Hospital of Wuhan University, Wuhan, Hubei 430071, P.R. China, Department of Immunology, School of Basic Medical Science, Wuhan University, Wuhan, Hubei 430071, P.R. China, Department of Laboratory Medicine, Zhongnan Hospital of Wuhan University, Wuhan, Hubei 430071, P.R. China
Published online on: September 3, 2025 https://doi.org/10.3892/or.2025.8982
Article Number: 149
Copyright: © Sun et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

T-cell acute lymphoblastic leukemia (T‑ALL) is an aggressive hematological malignancy. The poor prognosis of T‑ALL is closely associated with extensive leukemic infiltration into critical organs. Therefore, the mechanism underlying T‑ALL infiltration is worth investigating. Databases and clinical samples were utilized to examine drebrin 1 (DBN1) expression in T‑ALL. DBN1 knockdown cell lines were established by lentivirus transfection, and cell migration and invasion were examined using Transwell and Matrigel‑Transwell assays. The molecular mechanism was investigated by RNA sequencing and further validated at the molecular level. Reverse transcription‑quantitative PCR and western blotting were employed to examine the expression of downstream molecules following DBN1 knockdown, with subsequent rescue experiments. DBN1‑targeting microRNA (miR) predicted using bioinformatics websites was confirmed using dual‑luciferase assays. In T‑ALL cells, miRNA mimics transfection enabled functional validation, and investigations into the underlying molecular mechanisms encompassing rescue experiments. Clinical samples and publicly available databases revealed that DBN1 was upregulated in patients with T‑ALL patients. DBN1 knockdown significantly decreased the migration and invasion of T‑ALL cells in vitro. RNA sequencing revealed that downregulation of DBN1 could reduce Grb2‑associated binding protein 2 (GAB2) expression. Western blotting revealed that GAB2 expression, and PI3K/AKT and MAPK/ERK signaling were decreased in DBN1‑knockdown cells. GAB2 overexpression restored the phosphorylation of downstream effectors (AKT and ERK1/2). Bioinformatics and dual‑luciferase reporter experiments identified miR‑218‑5p binding to the 3'-untranslated region of DBN1, which suppressed DBN1 expression. In addition, the experiments demonstrated that miR‑218‑5p acted as an upstream regulator of DBN1, and was involved in cell migration and invasion. Overall, DBN1 was upregulated in T‑ALL, and its depletion inhibited cell migration and invasion through downregulation of GAB2 and consequent inhibition of AKT and ERK signaling cascades. The present data suggested that DBN1 could be a novel biomarker of T‑ALL infiltration, which is a novel perspective in the field of leukemia research.

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