BIRC6 (APOLLON) is down-regulated in acute myeloid leukemia and its knockdown attenuates neutrophil differentiation

Schläfli, Anna M.; Torbett, Bruce E.; Fey, Martin F.; Tschan, Mario P.

doi:10.1186/2162-3619-1-25

Cited by 9 publications

(6 citation statements)

References 24 publications

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“…This finding suggests that AHR is an important regulator of genes which control ROS detoxification, as Stra13 has been decreased in both AhR-KO and AhR Vav1 mice. Birc6 is a regulator of apoptosis and has been described as being deregulated in acute myeloid leukemia [ 44 ]. Interestingly, knockdown of Birc6 in cell lines used to model promyelytic leukemia impairs neutrophil differentiation, and AhR regulation of Birc6 is suggested by our data.…”

Section: Discussionmentioning

confidence: 99%

Conditional deletion of Ahr alters gene expression profiles in hematopoietic stem cells

Bennett

et al. 2018

PLoS ONE

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The aryl hydrocarbon receptor (AHR) is a ligand activated bHLH transcription factor that belongs to the Per-Arnt-Sim (PAS) superfamily of proteins involved in mediating responses to cellular environment regulating normal physiological and developmental pathways. The AHR binds a broad range of naturally derived and synthetic compounds, and plays a major role in mediating effects of certain environmental chemicals. Although our understanding of the physiological roles of the AHR in the immune system is evolving, there is little known about its role in hematopoiesis and hematopoietic diseases. Prior studies demonstrated that AHR null (AHR-KO) mice have impaired hematopoietic stem cell (HSC) function; they develop myeloproliferative changes in peripheral blood cells, and alterations in hematopoietic stem and progenitor cell populations in the bone marrow. We hypothesized mice lacking AHR expression only within hematopoietic cells (AHRVav1 mice) would develop similar changes. However, we did not observe a complete phenocopy of AHR-KO and AHRVav1 animals at 2 or 18 months of age. To illuminate the signaling mechanisms underlying the alterations in hematopoiesis observed in these mice, we sorted a population of cells highly enriched for HSC function (LSK cells: CD34-CD48-CD150+) and performed microarray analyses. Ingenuity Pathway and Gene Set Enrichment Analyses revealed that that loss of AHR within HSCs alters several gene and signaling networks important for HSC function. Differences in gene expression networks among HSCs from AHR-KO and AHRVav1 mice suggest that AHR in bone marrow stromal cells also contributes to HSC function. In addition, numerous studies have suggested a role for AHR in both regulation of hematopoietic cells, and in the development of blood diseases. More work is needed to define what these signals are, and how they act upon HSCs.

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Section: Discussionmentioning

confidence: 99%

Conditional deletion of Ahr alters gene expression profiles in hematopoietic stem cells

Bennett

et al. 2018

PLoS ONE

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“…PML-RARα is a potent transcriptional repressor in APL cells, and it blocks promyelocyte differentiation. An interesting characteristic of this oncogenic protein is that its transcriptional repression effects can be reverted with pharmacologic doses of ATRA, resulting in the reactivation of genes essential for definitive myeloid differentiation [ 2 , 3 , 25 ]. Recently, lncRNAs have been shown to be dysregulated in various cancers, and several lncRNAs have been functionally linked to cancer and cell differentiation [ 13 , 15 ].…”

Section: Discussionmentioning

confidence: 99%

Inhibition of long non-coding RNA NEAT1 impairs myeloid differentiation in acute promyelocytic leukemia cells

et al. 2014

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BackgroundAcute promyelocytic leukemia (APL) is characterized by the reciprocal translocation t(15;17), which fuses PML with retinoic acid receptor alpha (RARα). Although PML-RARα is crucially important for pathogenesis and responsiveness to treatment, the molecular and cellular mechanisms by which PML-RARα exerts its oncogenic potential have not been fully elucidated. Recent reports have suggested that long non-coding RNAs (lncRNAs) contribute to the precise control of gene expression and are involved in human diseases. Little is known about the role of lncRNA in APL.MethodsWe analyzed NEAT1 expression in APL samples and cell lines by real-time quantitative reverse transcription-PCR (qRT-PCR). The expression of PML-RARα was measured by Western blot. Cell differentiation was assessed by measuring the surface CD11b antigen expression by flow cytometry analysis.ResultsWe found that nuclear enriched abundant transcript 1 (NEAT1), a lncRNA essential for the formation of nuclear body paraspeckles, is significantly repressed in de novo APL samples compared with those of healthy donors. We further provide evidence that NEAT1 expression was repressed by PML-RARα. Furthermore, significant NEAT1 upregulation was observed during all-trans retinoic acid (ATRA)-induced NB4 cell differentiation. Finally, we demonstrate the importance of NEAT1 in myeloid differentiation. We show that reduction of NEAT1 by small interfering RNA (siRNA) blocks ATRA-induced differentiation.ConclusionsOur results indicate that reduced expression of the nuclear long noncoding RNA NEAT1 may play a role in the myeloid differentiation of APL cells.Electronic supplementary materialThe online version of this article (doi:10.1186/1471-2407-14-693) contains supplementary material, which is available to authorized users.

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“…Similar to the previous observations that BIRC6 upregulation was also resistant to various anticancer drug in different cancer cells 31,35–37 , the effect of miR-204 on apoptosis through BIRC6 was further confirmed in our study using BIRC6 plasmid in AML cells. However, a previous study reported that reduced BIRC6 expression was associated with an immature myeloid phenotype of AML samples rather than immature myeloid cells 38 . These apparent discrepancies may be related to different cell subtypes in distinct leukemic entities and must be reconciled by additional studies.…”

Section: Discussionmentioning

confidence: 89%

MicroRNA-204 Potentiates the Sensitivity of Acute Myeloid Leukemia Cells to Arsenic Trioxide

Wang

Fang

et al. 2019

oncol res

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Although arsenic trioxide (ATO) is a well-known antileukemic drug used for acute promyelocytic leukemia treatment, the development of ATO resistance is still a big challenge. We previously reported that microRNA-204 (miR-204) was involved in the regulation of acute myeloid leukemia (AML) cell apoptosis, but its role in chemoresistance is poorly understood. In the present study, we showed that miR-204 was significantly increased in AML cells after ATO treatment. Interestingly, the increased miR-204 level that was negatively correlated with ATO induced the decrease in cell viability and baculoviral inhibition of apoptosis protein repeat-containing 6 (BIRC6) expression. Overexpression of miR-204 potentiated ATO-induced AML cell growth inhibition and apoptosis. Furthermore, miR-204 directly targets to the 3′-UTR of BIRC6. Upregulation of miR-204 decreased BIRC6 luciferase activity and expression, which subsequently enhanced the expression of p53. Restoration of BIRC6 markedly reversed the effect of miR-204 on the regulation of AML cell sensitivity to ATO. Taken together, our study demonstrates that miR-204 decreases ATO chemoresistance in AML cells at least partially via promoting BIRC6/p53-mediated apoptosis. miR-204 represents a novel target of ATO, and upregulation of miR-204 may be a useful strategy to improve the efficacy of ATO in AML treatment.

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BIRC6 (APOLLON) is down-regulated in acute myeloid leukemia and its knockdown attenuates neutrophil differentiation

Cited by 9 publications

References 24 publications

Conditional deletion of Ahr alters gene expression profiles in hematopoietic stem cells

Conditional deletion of Ahr alters gene expression profiles in hematopoietic stem cells

Inhibition of long non-coding RNA NEAT1 impairs myeloid differentiation in acute promyelocytic leukemia cells

MicroRNA-204 Potentiates the Sensitivity of Acute Myeloid Leukemia Cells to Arsenic Trioxide

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