Background: Recent studies have revealed that long noncoding RNAs (lncRNAs) may hold crucial triggers of the pathogenesis of hematological malignancies, while the studies evaluating the expression pattern of lncRNA in acute myeloid leukemia (AML) are few. Thus, this study aimed to investigate the implication of lncRNA expression pattern in AML development and progression.
Methods: Bone marrow samples from four AML patients and four controls were subjected to lncRNA sequencing. Then, bone marrow samples from 110 AML patients and 40 controls were proposed to real-time quantitative polymerase chain reaction (RT-qPCR) validation for 10 candidate lncRNAs. Clinical data and survival profiles were recorded in AML patients. Furthermore, lncRNA RP4-576H24.2 expression in AML cell lines and its effect on AML cell proliferation and apoptosis were detected.
Results: LncRNA expression pattern by sequencing clearly distinguished AML patients from controls, and 630 upregulated and 621 downregulated lncRNAs were identified in AML patients compared to controls, which were mainly enriched in AML oncogene-related biological process and pathways (such as neutrophil degranulation, leukocyte transendothelial migration, and hematopoietic cell lineage). RT-qPCR validation observed that six lncRNAs correlated with AML risk, one lncRNA associated with risk stratification, and three lncRNAs correlated with survivals, among which lncRNA RP4-576H24.2 was the only one correlated with AML susceptibility, risk stratification, and survivals. Further in vitro experiments showed that lncRNA RP4-576H24.2 was upregulated in AML cell lines compared to normal bone marrow mononuclear cells (BMMCs), and promoted proliferation while inhibited apoptosis in HL-60 and KG-1 cells.
Conclusions: LncRNA expression pattern is closely involved in the development and progression of AML, and several specific lncRNAs exhibit potential to be biomarkers for AML risk and prognosis. Besides, lncRNA RP4-576H24.2 might be a potential oncogene in AML pathogenesis.
Keywords: acute myeloid leukemia; disease risk; lncRNA RP4-576H24.2; long noncoding RNA expression pattern; prognosis.
© 2019 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.