Zhong Yuan Academy of Biological Medicine, Liaocheng People's Hospital, Liaocheng, 252000, Shandong, People's Republic of China.
Key Laboratory for Pediatrics of Integrated Traditional and Western Medicine, Liaocheng People's Hospital, Liaocheng, 252000, Shandong, People's Republic of China.
Clin Exp Med. 2023 Jul;23(3):777-785. doi: 10.1007/s10238-022-00863-8. Epub 2022 Jul 22.
Previous studies have shown that the gene AT-rich interactive domain-containing protein 1A (ARID1A) is a subunit of SWI/SNF chromatin remodeling complex that acts as a tumor suppressor gene in several cancers and plays a vital role in tumorigenesis. However, its biological functions in acute myeloid leukemia (AML) are still unclear. Here, we tried to elaborate the expression of ARID1A in patients with AML, in leukemia cells, as well as the molecular mechanisms. Our results indicated that the expression of ARID1A was significantly downregulated in the bone marrow of patients with AML and relapsed patients compared with healthy subjects and patients in complete remission. Meantime, receiver operating characteristic curve analysis showed that the expression of ARID1A could be used to discriminate between patients with AML and patients in complete remission. We further constructed a knockdown cell model to determine the regulatory mechanisms of ARID1A in AML cells. We found that the decreased expression of ARID1A promoted cell proliferation, suppressed cellular apoptosis, and impeded cell cycle arrest via TGF-β1/SMAD3 signaling pathway. These results revealed that the reduced expression of ARID1A promoted cell proliferation via the TGF-β1/SMAD3 cascade and served as a prognostic biomarker for AML and therapeutic targets.
先前的研究表明，富含 AT 的相互作用结构域蛋白 1A（ARID1A）基因是 SWI/SNF 染色质重塑复合物的一个亚基，在几种癌症中作为抑癌基因发挥作用，在肿瘤发生中起着至关重要的作用。然而，其在急性髓细胞白血病（AML）中的生物学功能仍不清楚。在这里，我们试图阐述 ARID1A 在 AML 患者、白血病细胞中的表达情况，以及其分子机制。我们的结果表明，与健康受试者和完全缓解的患者相比，ARID1A 在 AML 患者和复发患者的骨髓中的表达显著下调。同时，受试者工作特征曲线分析表明，ARID1A 的表达可用于区分 AML 患者和完全缓解的患者。我们进一步构建了敲低细胞模型，以确定 ARID1A 在 AML 细胞中的调控机制。我们发现，ARID1A 的表达下调通过 TGF-β1/SMAD3 信号通路促进细胞增殖，抑制细胞凋亡，阻碍细胞周期停滞。这些结果表明，ARID1A 的表达减少通过 TGF-β1/SMAD3 级联促进细胞增殖，并可作为 AML 的预后生物标志物和治疗靶点。
