Long noncoding RNAs (lncRNAs) play important roles in diverse cellular processes and carcinogenesis. Homeobox A cluster antisense RNA 2 (HOXA‐AS2) is a 1,048‐basepairs lncRNA located between human HOXA3 and HOXA4 genes, whose overactivation was previously found to promote the proliferation and invasion of solid tumors. However, its clinical and biological roles in acute myeloid leukemia (AML) remain unclear. This study showed that HOXA‐AS2 was overexpressed in AML patients. In addition, the increased HOXA‐AS2 expression was correlated with higher white blood cell and bone marrow blast counts, unfavorable karyotype classification, more measurable residual disease positivity, and earlier death. There was also a tendency toward inferior survival in patients with high HOXA‐AS2 expression, and HOXA‐AS2 was an independent prognostic factor among the normal‐karyotype AMLs. Furthermore, the results of in vitro study showed that silencing HOXA‐AS2 significantly inhibited the growth of leukemic cells by inducing G1/G0‐phase arrest and apoptosis. Further analysis demonstrated that silencing HOXA‐AS2 suppressed the phosphorylation level of PI3K and AKT, which thereafter promoted the expression of P21 and P27. Moreover, it was suggested that the sex‐determining region Y‐box 4 (SOX4), which is closely involved in the PI3K/AKT pathway, might be one of the major downstream targets of HOXA‐AS2. Silencing HOXA‐AS2 decreased the expression of SOX4, whereas the upregulation of SOX4 partially abrogated the inhibitory effect of silencing HOXA‐AS2 on leukemic cells. In conclusion, these findings suggest that HOXA‐AS2 probably functions as an oncogene via SOX4/PI3K/AKT pathway and might be a useful biomarker for the prognostic prediction in AML patients, providing a potential therapeutic target for AML.

中文翻译：

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较长的非编码RNA HOXA-AS2的过表达预示了不良的预后，并通过SOX4 / PI3K / AKT途径促进了急性髓细胞白血病的肿瘤发生。

长的非编码RNA（lncRNA）在各种细胞过程和致癌作用中起重要作用。Homeobox簇反义RNA 2（HOXA-AS2）是位于人类HOXA3和HOXA4基因之间的1,048个碱基对的lncRNA，以前发现其过度激活会促进实体瘤的增殖和侵袭。但是，其在急性髓细胞性白血病（AML）中的临床和生物学作用仍不清楚。这项研究表明，HOXA-AS2在AML患者中过表达。此外，HOXA-AS2表达增加与白细胞和骨髓母细胞计数升高，核型分类不良，残留疾病阳性率更高，死亡更早有关。HOXA-AS2高表达患者的生存率也有下降的趋势，HOXA‐AS2是正常核型AML中的独立预后因素。此外，体外研究结果表明，沉默HOXA-AS2可诱导G1 / G0期阻滞和凋亡，从而显着抑制白血病细胞的生长。进一步的分析表明，沉默HOXA-AS2可抑制PI3K和AKT的磷酸化水平，此后可促进P21和P27的表达。此外，有人建议，与PI3K / AKT通路密切相关的性别决定区Y-box 4（SOX4）可能是HOXA-AS2的主要下游目标之一。沉默HOXA-AS2会降低SOX4的表达，而SOX4的上调部分消除了沉默HOXA-AS2对白血病细胞的抑制作用。结论，