Long Noncoding RNA HOXA-AS2 Functions as an Oncogene by Binding to EZH2 and Suppressing LATS2 in AML

Abstract

BackgroundLong noncoding RNAs (lncRNAs) plays 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 there are few reports on its role in Acute myeloid leukemia (AML). MethodsThe expression of HOXA-AS2 in AML cell line was detected by qRT-PCR. AML cases from the public database (GEPIA) were also included in this study. Cell counting kit-8 (CCK-8) assay, flow cytometry, immunofluorescence and Western blot were used to detect the role of HOXA-AS2 in AML cells. Luciferase reporter gene detection, RIP, RNA pull-down and RNA-ChIP detection were used to demonstrate the molecular biological mechanism of HOXA-AS2 in AML.ResultsOur results show that 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. After overexpressing HOXA-AS2, it will show the opposite result. Moreover, more in-depth mechanism studies show that HOXA-AS2 exerts its carcinogenicity mainly by binding with the epigenetic inhibitor Enhancer of zeste homolog 2 (EZH2) and then inhibiting the expression of Large Tumor Suppressor 2 (LATS2). ConclusionsTaken together, our results highlight the important role of HOXA-AS2 in AML, suggesting that HOXA-AS2 may be an effective therapeutic target for patients with AML.