Myelodysplastic syndrome (MDS) is a heterogeneously cloned hematopoietic stem cell malignancy with a high risk of developing acute myeloid leukemia (AML). 4-amino-2-trifluoromethyl-phenyl resinate (ATPR), a novel all-trans retinoic acid (ATRA) derivative designed in our group, was proved to be a tumor inhibitor in diverse types of cancer cells in vitro. However, little has been known about the effects of ATPR on MDS. To analyze if and to what extent it's anti-tumor activity on MDS, we performed CCK-8, Flow Cytometry, Wright-Giemsa staining, qRT-PCR, and Western blot to analyze the SKM-1 cells state after ATPR treatment in multiplex detection angles. As expected, our results proved that ATPR could effectively induce cell differentiation and reduce cell proliferation of SKM-1 cell lines. Subsequently, to further analyze the potential mechanisms, we applied Label-free proteomic techniques to discover relevant protein that may be involved. Most notably, a series of factors related to RNA behavioral regulation were changed. Among them, we demonstrated that DEAD-box RNA helicase DDX23 was abnormally ablated in MDS patients and could be restored after ATPR treatment in vitro. Besides, our results suggested that ATPR-induced SKM-1 cell maturation was counteracted when knockdown DDX23, underscoring that DDX23 might be involved. In conclusion, we confirmed that ATPR could induce SKM-1 cells differentiation and its positive influence of DDX23 may provide a new idea to relieve MDS.

中文翻译：

---

4-氨基-2-三氟甲基-苯基视黄酸酯通过上调DDX23诱导人骨髓增生异常综合症SKM-1细胞系的分化。

骨髓增生异常综合症（MDS）是异源克隆的造血干细胞恶性肿瘤，具有发展为急性髓细胞性白血病（AML）的高风险。4-氨基-2-三氟甲基-苯基树脂酸酯（ATPR）是我们小组设计的新型全反式维甲酸（ATRA）衍生物，被证明是体外多种癌细胞中的肿瘤抑制剂。但是，关于ATPR对MDS的影响知之甚少。为了分析其对MDS的抗肿瘤活性以及在何种程度上具有抗肿瘤活性，我们进行了CCK-8，流式细胞术，Wright-Giemsa染色，qRT-PCR和Western印迹分析以多重检测ATPR处理后的SKM-1细胞状态角度。如预期的那样，我们的结果证明ATPR可以有效诱导细胞分化并减少SKM-1细胞系的细胞增殖。随后，为了进一步分析潜在的机制，我们应用了无标签蛋白质组学技术来发现可能涉及的相关蛋白质。最值得注意的是，与RNA行为调控有关的一系列因素发生了变化。其中，我们证明了DEDS-box RNA解旋酶DDX23在MDS患者中被异常消融，并且在体外ATPR治疗后可以恢复。此外，我们的结果表明，当敲低DDX23时，ATPR诱导的SKM-1细胞成熟被抵消了，强调了可能参与了DDX23。总之，我们证实ATPR可以诱导SKM-1细胞分化，而DDX23的积极影响可能为缓解MDS提供了新的思路。我们证明了DEDS-box RNA解旋酶DDX23在MDS患者中被异常消融，并且在体外ATPR治疗后可以恢复。此外，我们的结果表明，当敲低DDX23时，ATPR诱导的SKM-1细胞成熟被抵消了，强调了可能参与了DDX23。总之，我们证实ATPR可以诱导SKM-1细胞分化，而DDX23的积极影响可能为缓解MDS提供了新的思路。我们证明了DEDS-box RNA解旋酶DDX23在MDS患者中被异常消融，并且在体外ATPR治疗后可以恢复。此外，我们的结果表明，当敲低DDX23时，ATPR诱导的SKM-1细胞成熟被抵消了，强调了可能参与了DDX23。总之，我们证实ATPR可以诱导SKM-1细胞分化，而DDX23的积极影响可能为缓解MDS提供了新的思路。