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.
Highlights
Introduction The two main features ofAcute myeloid leukemia (AML) are uncontrolled malignant proliferation and blocked differentiation, accounting for 30% of leukemia related deaths[1,2]
HOXA-AS2 levels were increased in AML In order to explore the role of HOXA-AS2 in AML, we first used GEPIA database to analyze the expression of HOXA-AS2 in AML patients
Kaplan–Meier survival analysis showed that the overall survival rate of AML patients with high expression of HOXA-AS2 (n = 53) was significantly lower than the patients with low expression of HOXA-AS2 (n = 53) (Fig. 1b). qRT-PCR results showed that HOXA-AS2 was highly expressed in many leukemia cell lines (KG-1, NB4, U937, HL-60, and THP-1 cells) compared to the normal human monocytes (Fig. 1c)
Summary
AML are uncontrolled malignant proliferation and blocked differentiation, accounting for 30% of leukemia related deaths[1,2]. AML patients after treatment, the condition has been greatly improved, but the prognosis of many patients is still not ideal. As a new noncoding RNA molecule, the abnormal expression of lncRNA in tumor tissue has attracted extensive attention of researchers[13,14]. Many studies have shown that lncRNA is likely to be a carcinogen gene[15,16] or a tumor suppressor gene[16] in the occurrence and development of tumors, and has increasingly become a biomarker of tumor diagnosis, treatment, or prognosis, including AML17,18.
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