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
Journal
BMC Cancer
Journal Volume
19
Journal Issue
1
Date Issued
2019
Author(s)
Chen F.-Y.
Lin C.-T.
Li C.-C.
Tseng M.-H.
Chen R.-H.
Abstract
Background: Long 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. Methods: shRNAs 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. Results: Downregulation 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. Conclusions: This 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. ? 2019 The Author(s).
SDGs
Other Subjects
azacitidine; cytarabine; decitabine; idarubicin; long untranslated RNA; long untranslated RNA HOXB AS3; mitoxantrone; unclassified drug; homeodomain protein; long untranslated RNA; tumor marker; acute myeloid leukemia; adult; allogeneic hematopoietic stem cell transplantation; Article; bone marrow cell; BrdU assay; cancer prognosis; cell cycle progression; cell proliferation; cohort analysis; consolidation chemotherapy; controlled study; DNA replication; down regulation; drug megadose; Hox gene; human; human cell; major clinical study; microarray analysis; middle aged; multiple cycle treatment; myelodysplastic syndrome; overall survival; polymerase chain reaction; prognosis; quantitative analysis; recurrence free survival; retrospective study; acute myeloid leukemia; adolescent; aged; bone marrow cell; cell cycle; cell proliferation; female; follow up; gene expression regulation; genetics; homeobox; Kaplan Meier method; male; metabolism; myelodysplastic syndrome; prognosis; tumor cell line; very elderly; young adult; Adolescent; Adult; Aged; Aged, 80 and over; Biomarkers, Tumor; Cell Cycle; Cell Line, Tumor; Cell Proliferation; DNA Replication; Female; Follow-Up Studies; Gene Expression Regulation, Leukemic; Genes, Homeobox; Homeodomain Proteins; Humans; Kaplan-Meier Estimate; Leukemia, Myeloid, Acute; Male; Middle Aged; Myelodysplastic Syndromes; Myeloid Cells; Prognosis; Retrospective Studies; RNA, Long Noncoding; Young Adult
Publisher
BioMed Central Ltd.
Type
journal article