Long noncoding RNA HOXA-AS2 functions as an oncogene by binding to EZH2 and suppressing LATS2 in acute myeloid leukemia (AML)

Abstract

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.