Affiliations: Department of Hematology, Huangshan City People’s Hospital, 4 Liyuan Road, Huangshan, Anhui 245000, China | Tel.: +86 13955951995; E-mail: [email protected]
Correspondence:
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Corresponding author: Department of Hematology, Huangshan City People’s Hospital, 4 Liyuan Road, Huangshan, Anhui 245000, China. Tel.: +86 13955951995; E-mail: [email protected].
Abstract: OBJECTIVE: The aim of this work was to extensively explore the long non-coding RNA (lncRNA) expression profiles in acute myeloid leukemia (AML) and to propose candidate lncRNAs with predictive value for AML risk. METHODS: The bone marrow mononuclear cell samples from 10 AML patients and 10 age and gender matched controls were obtained and subjected to next-generation RNA sequencing. Then, the top 5 upregulated and top 5 downregulated lncRNAs in AML patients compared with controls were selected for further quantitative polymerase chain reaction (qPCR) validation in 40 AML patients and 40 age and gender matched controls. The effect of candidate lncRNA RP11-342M1.7 on proliferation and apoptosis in AML cells was further investigated. RESULTS: RNA sequencing observed 216 upregulated and 412 downregulated lncRNAs in AML patients compared with controls. Enrichment analyses exhibited that these differentially expressed lncRNAs were involved in neoplastic signaling pathways such as cAMP and MAPK signaling pathways. In further qPCR validation, lncRNA RP11-342M1.7 and lncRNA CDCA4P3 were upregulated, while lncRNA CES1P1, lncRNA AC008753.6 and lncRNA RP11-573G6.10 were downregulated in AML patients compared with controls. Multivariate logistic regression analysis disclosed that lncRNA RP11-342M1.7, lncRNA CES1P1 and lncRNA AC008753.6 were independent predictive factors for AML risk, and most importantly, the combination of these three lncRNAs was of remarkably good predictive value for AML risk (AUC: 0.901; 95% CI: 0.835–0.966). Besides, lncRNA RP11-342M1.7 was correlated with higher CR while lncRNA AC008753.6 and lncRNA CTD-2562J15.6 were correlated with lower CR. LncRNA RP11-342M1.7 knockdown suppressed cell proliferation by promoting cell apoptosis in AML cells. CONCLUSIONS: This study reveals the comprehensive lncRNAs expression profiles in AML, and proposes candidate lncRNAs that are potential biomarkers for AML risk.
Keywords: AML risk, expression profiles, long non-coding RNA, predictive value, RNA sequencing
