Actin-like 6A (ACTL6A), a component of BAF chromatin remodeling complexes, is important for cell differentiation. Nevertheless, its role and mechanism in acute promyelocytic leukemia (APL) has not been reported. To identify the genes that may participate in the development of APL, we analyzed data from an APL cDNA microarray (GSE12662) in the NCBI database, and found that ACTL6A was up-regulated in APL patients. Subsequently, we investigated the function and mechanisms of ACTL6A in myeloid cell development. The expression of ACTL6A was gradually decreased during granulocytic differentiation in all-trans retinoic acid-treated NB4 and HL-60 cells, and phorbol myristate acetate-treated HL-60 cells. We also found that knockdown of ACTL6A promoted differentiation in NB4 and HL-60 cells, and decreased the levels of Sox2 and Notch1. Mechanistically, ACTL6A interacted with and was co-localized with Sox2 and p53. Meanwhile, CBL0137, an activator of p53, decreased the expression of ACTL6A and promoted differentiation in NB4 and HL-60 cells. These findings suggest that the inhibition of ACTL6A promotes differentiation via the Sox2 and Notch1 signaling pathways. Furthermore, the differentiation promoted by inhibiting ACTL6A could be regulated by p53 via its physical interaction with ACTL6A.

中文翻译：

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ACTL6A与急性早幼粒细胞白血病细胞系中的p53相互作用，以通过Sox2 / Notch1信号通路影响分化。

肌动蛋白样6A（ACTL6A）是BAF染色质重塑复合物的组成部分，对细胞分化很重要。然而，尚未报道其在急性早幼粒细胞白血病（APL）中的作用和机制。为了鉴定可能参与APL发育的基因，我们分析了NCBI数据库中来自APL cDNA微阵列（GSE12662）的数据，发现ACTL6A在APL患者中上调。随后，我们研究了ACTL6A在骨髓细胞发育中的功能和机制。在全反式维甲酸处理的NB4和HL-60细胞和佛波肉豆蔻酸酯乙酸盐处理的HL-60细胞的粒细胞分化过程中，ACTL6A的表达逐渐降低。我们还发现，敲低ACTL6A可以促进NB4和HL-60细胞的分化，并降低Sox2和Notch1的水平。机械上，ACTL6A与Sox2和p53相互作用并与它们共定位。同时，p53的激活剂CBL0137降低了ACTL6A的表达并促进了NB4和HL-60细胞的分化。这些发现表明，抑制ACTL6A可以通过Sox2和Notch1信号通路促进分化。此外，通过抑制ACTL6A促进的分化可以通过p53与ACTL6A的物理相互作用来调节。