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

Huang, Huai-Hsuan; Chen, Fei-Yun; Chou, Wen‐Chien; Hou, Hsin‐An; Ko, Bor‐Sheng; Lin, Chun‐Chi; Tang, Jih‐Luh; Li, Chi‐Cheng; Yao, Ming; Tsay, Woei; Hsu, Szu-Chun; Wu, Shang‐Ju; Chen, Chien-Yuan; Huang, Shang-Yi; Tseng, Mei‐Hsuan; Tien, Hwei‐Fang; Chen, Ruey‐Hwa

doi:10.1186/s12885-019-5822-y

Cited by 53 publications

(42 citation statements)

References 48 publications

(58 reference statements)

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“…In addition, down regulation of HOXB-AS3 can inhibit cell proliferation. In AML, patients with high HOXB-AS3 expression have shorter survival than patients with low HOXB-AS3 expression [35]. More than 30% of AML patients have a type III receptor tyrosine kinase FLT3 mutation, and HOXB2 and HOXB3 are novel regulators of oncogenic FLT3-ITD-driven AML [36].…”

Section: Discussionmentioning

confidence: 99%

Identification of acute myeloid leukemia-driven genes by multi-dimensional approach

Jian

Hao

Liu

et al. 2020

Preprint

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Background Acute myeloid leukemia (AML), which is characterized by the uncontrolled proliferation of myeloid leukemia cells in the bone marrow and other hematopoietic tissues, and is highly heterogeneous. While with the progress of sequencing technology, understanding of the AML-related biomarkers are still incomplete. The purpose of this study is to identify potential biomarkers for diagnosis of AML. Methods Based on WGCNA analysis of gene mutation expression, methylation level distribution, mRNA expression and AML-related genes in public databases, were employed for investigating potential biomarkers for prognosis of AML. Results This study screened a total of 6,383 genes by analyzing various changes in 103 acute myeloid leukemia (AML) samples, including gene mutation expression, methylation level distribution, mRNA expression, and AML-related genes in public databases. Moreover, seven AML-related co-expression modules were mined by WGCNA analysis and twelve biomarkers associated with the AML prognosis were identified from each top 10 genes of the seven co-expression modules. The AML samples were then classified into two subgroups, the prognosis of which is significantly different, based on the expression of these twelve genes. The differentially expr essed genes are mainly involved in glucose metabolism, glutathione biosynthesis, small G protein-mediated signal transduction, and the Rap1 signaling pathway. Conclusions With the utilization of WGCNA mining, seven gene co-expression modules were identified from TCGA database and there are unreported genes that may as potential driven genes of AML and may be the direction to identify the possible molecular signatures to predict survival of AML patients and help guide experiments for potential clinical drag targets.

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Section: Discussionmentioning

confidence: 99%

Identification of acute myeloid leukemia-driven genes by multi-dimensional approach

Jian

Hao

Liu

et al. 2020

Preprint

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“…In addition, a recent study reports that lncRNA in nonhomologous end joining (NHEJ) pathway 1 (LINP1) is upregulated in pediatric and adolescent AML patients, and promotes the malignant behaviors in AML cells via regulating the HNF4α/AMPK/WNT5A signaling pathway . Another study illuminates that lncRNA HOXB‐AS3 enhances AML cell proliferation and its elevated expression predicts worse prognosis patients with AML and myelodysplastic syndrome . While the systemic investigation of multiple lncRNAs as biomarkers for AML risk and prognosis is not conducted yet.…”

Section: Discussionmentioning

confidence: 99%

“…26 Another study illuminates that lncRNA HOXB-AS3 enhances AML cell proliferation and its elevated expression predicts worse prognosis patients with AML and myelodysplastic syndrome. 27 While the systemic investigation of multiple lncRNAs as biomarkers for AML risk and prognosis is not conducted yet. In our study, 10 candidate lncRNAs that were selected from RNA sequencing results were further validated by RT-qPCR in 110 AML patients and 40 controls, and their correlations with disease risk and prognosis were assessed, which elucidated that there were six candidate lncRNAs correlated with AML risk, LncRNAs, median (IQR)…”

Section: Discussionmentioning

confidence: 99%

The implication of lncRNA expression pattern and potential function of lncRNA RP4‐576H24.2 in acute myeloid leukemia

Jian

Yuan

et al. 2019

Cancer Medicine

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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.

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“…Myelodysplastic syndromes (MDS) is a group of ineffective hematopoiesis hemopathies disorders characterized by defects in differentiation of hematopoietic precursor and amplification of the abnormal clones [1][2][3][4]. MDS is usually a rare group of "bone marrow failure disorder" that is not recognized and diagnosed.…”

Section: Introductionmentioning

confidence: 99%

LINC01255 combined with BMI1 to regulate Human Mesenchymal Stromal Senescence and Acute myeloid leukemia cell proliferation through repress the transcription of MCP-1

Liu

Dong

et al. 2020

Preprint

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Background: Long non-coding RNAs (lncRNAs) govern fundamental biochemical and cellular biology processes, for example, participate in chromatin remodeling, imprinting, splicing, transcriptional regulation and translation. Dysregulation of lncRNA expression is act as a feature of various diseases and cancers, including hematopoietic malignancies. However, the clinical relevance of myelodysplastic syndrome (MDS) and acute myeloid leukemia preceded by MDS (MDS-AML) requires further research. Recently, lncRNAs have been demonstrated plays an important role in hematopoiesis, thus, to further finding more functional lncRNA seemed particularly important.Methods: Western blotting, real-time PCR, RNA-pulldown, RIP, Chromatin immunoprecipitation (ChIP), cellular compartments extraction assays, SA-β-gal staining, lentivirus transfection, cell viability assay and cell proliferation assays were used to examine the relationship between lncRNA LINC01255 and its regulation of p53-p21 pathway in human mesenchymal stromal and acute myeloid leukemia cells.Results: LncRNA LINC01255 is highly expressed in bone marrow cells of AML patients, CD34+ cells of MDS-AML patients and AML cell lines and the higher expression of LINC01255 is assocoated with poor survival rate of AML patients. LINC01255 can interact with BMI1 and repress the transcription of MCP-1 to active p53-p21 pathway, thus inhibiting the senescence of human mesenchymal stromal and proliferation of acute myeloid leukemia cell.Conclusions: We discovered a novel functional lncRNA LINC01255, which can regulate the senescence of human mesenchymal stromal and the proliferation of acute myeloid leukemia cell through inhibiting the transcription of MCP-1.

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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

Cited by 53 publications

References 48 publications

Identification of acute myeloid leukemia-driven genes by multi-dimensional approach

Identification of acute myeloid leukemia-driven genes by multi-dimensional approach

The implication of lncRNA expression pattern and potential function of lncRNA RP4‐576H24.2 in acute myeloid leukemia

LINC01255 combined with BMI1 to regulate Human Mesenchymal Stromal Senescence and Acute myeloid leukemia cell proliferation through repress the transcription of MCP-1

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