Regulatory role of RBM39 in acute myeloid leukemia: Mediation through the PI3K/AKT pathway.

Xiaoyan Zhang, Lin Yang, Xiaojun Liu, Ziyuan Nie, Menghan Liu, Tianyang Wang, Yaqiong Lu, Yuxia Pan, Ying Zhan, Zhenzhen Wang, Jianmin Luo

Biochimica et biophysica acta. Molecular cell research 2024 Jan

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Acute myeloid leukemia (AML) presents ongoing therapeutic challenges due to its intricate molecular pathogenesis. This study aimed to elucidate the role of RNA binding motif protein 39 (RBM39) in AML cell proliferation, apoptosis, and chemosensitivity, and its potential modulation of the PI3K/AKT pathway. In vitro and in vivo experiments were conducted using AML cell lines (K562 and U937) and bone marrow mononuclear cells (BM-MNCs) from AML patients and healthy donors. RBM39 mRNA and protein levels were measured using qRT-PCR and Western blotting. Cells were transfected with sh-RBM39 or sh-control, and then treated with daunorubicin (DNR) or homoharringtonine (HHT) at varied concentrations. Cell proliferation, chemosensitivity, and apoptosis were assessed through CCK-8 assay and Annexin V-APC/PI staining. RNA sequencing identified differentially expressed genes (DEGs) post RBM39 knockdown. An in vivo xenograft AML model using E7070, a selective RBM39 inhibitor, was employed to evaluate RBM39 modulation effects. Elevated RBM39 levels were found in AML patients and cell lines compared to controls. RBM39 knockdown promoted apoptosis, curtailed cell proliferation, and enhanced chemosensitivity to DNR and HHT in vitro. Drug-resistant or relapsed AML patients displayed higher RBM39 levels. RNA sequencing after RBM39 knockdown revealed downregulated PI3K/AKT signaling. The xenograft model validated in vitro results, as E7070 treatment suppressed AML xenograft growth via RBM39-mediated PI3K/AKT pathway suppression. RBM39 plays a pivotal role in AML progression through the PI3K/AKT signaling pathway. Targeting RBM39, potentially with E7070, could inhibit proliferation and induce apoptosis in AML cells, offering a promising avenue for future AML research and treatment. Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.

Citation

Xiaoyan Zhang, Lin Yang, Xiaojun Liu, Ziyuan Nie, Menghan Liu, Tianyang Wang, Yaqiong Lu, Yuxia Pan, Ying Zhan, Zhenzhen Wang, Jianmin Luo. Regulatory role of RBM39 in acute myeloid leukemia: Mediation through the PI3K/AKT pathway. Biochimica et biophysica acta. Molecular cell research. 2024 Jan;1871(1):119607