Inflammation and Immune Mediated Diseases Laboratory of Anhui Province, School of Pharmacy, Anhui Medical University, Hefei, Anhui, China.
The Key Laboratory of Anti-inflammatory and Immune Medicines, Ministry of Education, Hefei, Anhui, China.
Cell Death Dis. 2020 Dec 2;11(12):1025. doi: 10.1038/s41419-020-03193-3.
Acute myeloid leukemia (AML) is the most common hematological malignancy in the world. Long noncoding RNAs (lncRNAs) play an important role in the development of physiology and pathology. Many reports have shown that lncRNA HOXA cluster antisense RNA 2 (HOXA-AS2) is a carcinogen and plays an important role in many tumors, but little is known about its role in AML. The aim of this study was to explore the potential mechanism and role of HOXA-AS2 in AML. HOXA-AS2 was upregulated in AML cell lines and tissues, and the overexpression of HOXA-AS2 is negatively correlated with the survival of patients. Silencing HOXA-AS2 can inhibit the proliferation and induce differentiation of AML cells in vitro and in vivo. Overexpressing HOXA-AS2 showed the opposite result. Moreover, more in-depth mechanism studies showed that carcinogenicity of HOXA-AS2 exerted mainly through binding with the epigenetic inhibitor Enhancer of zeste homolog 2 (EZH2) and then inhibiting the expression of Large Tumor Suppressor 2 (LATS2). Taken together, our findings highlight the important role of HOXA-AS2 in AML, suggesting that HOXA-AS2 may be an effective therapeutic target for patients with AML.
急性髓系白血病（AML）是世界上最常见的血液系统恶性肿瘤。长链非编码 RNA（lncRNA）在生理和病理发展中发挥重要作用。许多报道表明，HOXA 簇反义 RNA2（HOXA-AS2）是一种致癌基因，在许多肿瘤中发挥重要作用，但对其在 AML 中的作用知之甚少。本研究旨在探讨 HOXA-AS2 在 AML 中的潜在机制和作用。HOXA-AS2 在 AML 细胞系和组织中上调，HOXA-AS2 的过表达与患者的生存呈负相关。沉默 HOXA-AS2 可抑制 AML 细胞在体外和体内的增殖并诱导其分化。过表达 HOXA-AS2 则显示出相反的结果。此外，更深入的机制研究表明，HOXA-AS2 的致癌作用主要是通过与表观遗传抑制剂 Enhancer of zeste homolog 2（EZH2）结合，然后抑制 Large Tumor Suppressor 2（LATS2）的表达来发挥的。综上所述，我们的研究结果强调了 HOXA-AS2 在 AML 中的重要作用，表明 HOXA-AS2 可能是 AML 患者的有效治疗靶点。
