ABSTRACT Acute myeloid leukemia (AML) is the most common type of leukemia in adults. Owing to the chemotherapy associated side effects and toxicity, it is necessary to find a new mechanism, which can identify new potential therapeutic targets at the molecular level. Here, we identified new target genes that are induced during the TPA-induced HL-60 cell differentiation by ChIP-seq and microarray data analysis. Using q-PCR and ChIP assay, we confirmed that the target genes including USP3, USP35, TCF4, and SGK1 are upregulated during TPA-mediated HL-60 cell differentiation. Levels of USP3, one of the deubiquitinating enzymes (DUBs), increased by TPA treatment, resulting in the reduction of H2AK119ub levels. In addition, we revealed that depletion of USP3 inhibits TPA-mediated leukemia cell differentiation q-PCR and FACS analysis. Taken together, our data indicate that USP3 promotes TPA-mediated leukemia cell differentiation via regulating H2AK119ub levels.

中文翻译：

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泛素特异性肽酶 3 通过调节 H2AK119ub 诱导 TPA 介导的白血病细胞分化

摘要 急性髓系白血病 (AML) 是成人中最常见的白血病类型。由于化疗相关的副作用和毒性，有必要找到一种新的机制，可以在分子水平上识别新的潜在治疗靶点。在这里，我们通过 ChIP-seq 和微阵列数据分析确定了在 TPA 诱导的 HL-60 细胞分化过程中诱导的新靶基因。使用 q-PCR 和 ChIP 测定，我们证实了包括 USP3、USP35、TCF4 和 SGK1 在内的靶基因在 TPA 介导的 HL-60 细胞分化过程中上调。USP3 是一种去泛素化酶 (DUB)，通过 TPA 处理增加，导致 H2AK119ub 水平降低。此外，我们发现 USP3 的消耗会抑制 TPA 介导的白血病细胞分化 q-PCR 和 FACS 分析。综合起来，