Abstract
BackgroundRecent 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.MethodsBone 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.ResultsLncRNA 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.ConclusionsLncRNA 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.
Highlights
Acute myeloid leukemia (AML), a complex hematological malignancy characterized by its heterogenetic cytology, presents poor long‐term outcome in the majority of adult patients.[1]
Another previous study performs whole‐genome microarrays in extramedullary infiltration (EMI) acute myeloid leukemia (AML) patients and non‐EMI AML patients, and discloses that 253 circular RNAs and 663 mRNAs are upregulated, but 259 circRNAs and 838 mRNAs are downregulated in EMI AML patients compared to non‐EMI AML patients, further enrichment analysis finds that these dysregulated circRNAs and mRNAs are mainly enriched in cell adhesion, migration, signal transduction, and cell to cell communications.[21]
A previous study using microarray and bioinformatics analyses reveals that in pediatric AML patients, 372 long noncoding RNAs (lncRNAs) and 136 mRNAs are found to be dysregulated in patients compared with normal controls, and further real‐time quantitative polymerase chain reaction (RT‐qPCR) validates that the most dysregulated lncRNAs in pediatric AML patients is lnc RNA ENST00000435695.22 And, another study assessing the lncRNA expression profile in cytogenetically normal AML patients observes a specific lncRNA expression profile which is dependent on the mutational status of nucleophosmin 1 (NPM1) gene, and finds 12 lncRNAs being able to distinguish NPM1‐mutated patients from NPM1 wild‐type patients; in addition, they discover that lncRNA XLOC_109948 is associated with drug resistance and prognosis.[23]
Summary
Acute myeloid leukemia (AML), a complex hematological malignancy characterized by its heterogenetic cytology, presents poor long‐term outcome in the majority of adult patients.[1]. Long noncoding RNA (lncRNA) is a class of RNAs with more than 200 nucleotides which have less protein‐coding capacities, those molecules function as key regulators in cellular activities (such as the process of cell cycle, differentiation, and imprinting).[5,6,7,8,9] Recent studies have revealed that lncRNAs may hold crucial triggers of the development and progression of hematological malignancies.[10] In AML, the studies aiming at investigating the role of lncRNA are limited, while the findings are minimal yet intriguing. We conducted this study to investigate the implication of lncRNA expression pattern in AML pathogenesis and the potential of several specific candidate lncRNAs as markers for AML risk and prognosis, and further explore the effect of lncRNA RP4‐576H24.2 on regulating AML progression
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