Long non-coding RNA HOXB-AS3 promotes myeloid cell proliferation and its higher expression is an adverse prognostic marker in patients with acute myeloid leukemia and myelodysplastic syndrome

BMC Cancer

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[1] 0000 0001 2287 1366, grid.28665.3f, Institute of Biological Chemistry, Academia Sinica, Taipei, Taiwan;0000 0004 0546 0241, grid.19188.39, Department of Laboratory Medicine, National Taiwan University Hospital, National Taiwan University, Taipei, Taiwan;0000 0004 0546 0241, grid.19188.39, Doctoral Degree Program in Translational Medicine, National Taiwan University and Academia Sinica, Taipei, Taiwan;0000 0001 2287 1366, grid.28665.3f, Institute of Biological Chemistry, Academia Sinica, Taipei, Taiwan;0000 0004 0546 0241, grid.19188.39, Taicheng Stem Cell Therapy Center, National Taiwan University, Taipei, Taiwan;0000 0004 0572 7815, grid.412094.a, Division of Hematology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan;0000 0004 0572 7815, grid.412094.a, Division of Hematology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan;0000 0004 0546 0241, grid.19188.39, Department of Laboratory Medicine, National Taiwan University Hospital, National Taiwan University, Taipei, Taiwan;0000 0004 0572 7815, grid.412094.a, Division of Hematology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan;0000 0004 0546 0241, grid.19188.39, Doctoral Degree Program in Translational Medicine, National Taiwan University and Academia Sinica, Taipei, Taiwan;0000 0004 0572 7815, grid.412094.a, Division of Hematology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan;0000 0004 0546 0241, grid.19188.39, Taicheng Stem Cell Therapy Center, National Taiwan University, Taipei, Taiwan;

关键词: HOXB-AS3;    Acute myeloid leukemia;    Myelodysplastic syndrome;   

DOI  :  10.1186/s12885-019-5822-y

来源: publisher

【 摘 要 】

BackgroundLong non-coding RNAs (lncRNAs) represent the majority of cellular transcripts and play pivotal roles in hematopoiesis. However, their clinical relevance in acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) remains largely unknown. Here, we investigated the functions of HOXB-AS3, a lncRNA located at human HOXB cluster, in the myeloid cells, and analyzed the prognostic significances in patients with AML and MDS.MethodsshRNAs were used to downregulate HOXB-AS3 in the cell lines and the effect was evaluated by quantitative polymerase chain reaction. The proliferation of the cell lines was illustrated by proliferation and BrdU flow assays. Further, we retrospectively analyzed the HOXB-AS3 expression in 193 patients with AML and 157 with MDS by microarray analysis, and evaluated its clinical importance.ResultsDownregulation of HOXB-AS3 suppressed cell proliferation. Mechanistically, HOXB-AS3 potentiated the expressions of several key factors in cell cycle progression and DNA replication without affecting the expressions of HOX genes. In AML, patients with higher HOXB-AS3 expression had shorter survival than those with lower HOXB-AS3 expression (median overall survival (OS), 17.7 months versus not reached, P <  0.0001; median relapse-free survival, 12.9 months versus not reached, P = 0.0070). In MDS, patients with higher HOXB-AS3 expression also had adverse prognosis compared with those with lower HOXB-AS3 expression (median OS, 14.6 months versus 42.4 months, P = 0.0018). The prognostic significance of HOXB-AS3 expression was validated in the TCGA AML cohort and another MDS cohort from our institute. The subgroup analyses in MDS patients showed that higher HOXB-AS3 expressions could predict poor prognosis only in lower-risk (median OS, 29.2 months versus 77.3 months, P = 0.0194), but not higher-risk group.ConclusionsThis study uncovers a promoting role of HOXB-AS3 in myeloid malignancies and identifies the prognostic value of HOXB-AS3 expression in AML and MDS patients, particularly in the lower-risk group.

【 授权许可】

CC BY