MicroRNAs in the pathogenesis of myelodysplastic syndromes and myeloid leukaemia

Song, Su Jung; Pandolfi, Pier Paolo

doi:10.1097/moh.0000000000000054

Cited by 13 publications

(8 citation statements)

References 58 publications

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“…A global imbalance of miRNA expression (and function) was reported in both solid and hematological malignancies 4 including acute myeloid leukemia (AML). 5 AML includes genetically diverse malignancies characterized by frequent chromosome translocations and variable response to treatment.…”

Section: Introductionmentioning

confidence: 99%

miR-194-5p/BCLAF1 deregulation in AML tumorigenesis

et al. 2017

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Deregulation of epigenetic mechanisms, including microRNA, contributes to leukemogenesis and drug resistance by interfering with cancer-specific molecular pathways. Here, we show that the balance between miR-194-5p and its newly discovered target BCL2-associated transcription factor 1 (BCLAF1) regulates differentiation and survival of normal hematopoietic progenitors. In acute myeloid leukemias this balance is perturbed, locking cells into an immature, potentially ‘immortal’ state. Enhanced expression of miR-194-5p by treatment with the histone deacetylase inhibitor SAHA or by exogenous miR-194-5p expression re-sensitizes cells to differentiation and apoptosis by inducing BCLAF1 to shuttle between nucleus and cytosol. miR-194-5p/BCLAF1 balance was found commonly deregulated in 60 primary acute myeloid leukemia patients and was largely restored by ex vivo SAHA treatment. Our findings link treatment responsiveness to re-instatement of miR-194-5p/BCLAF1 balance.

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Section: Introductionmentioning

confidence: 99%

miR-194-5p/BCLAF1 deregulation in AML tumorigenesis

et al. 2017

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“…Among master regulators of these programs are miRNAs that direct early multipotential progenitor cells to adopt a certain cell fate program mainly by controlling the precise timing and expression levels of key factors and conferring robustness to regulative networks (O'Connell and Baltimore, ). Particularly, studies carried out during the past few years have shown a key role of some miRNAs in the control of self‐renewal of HSCs and their deregulation was involved in the transformation of HSCs and in the generation of leukemias (Sing and Pandolfi, ).…”

Section: Discussionmentioning

confidence: 99%

A miRNA Signature in Human Cord Blood Stem and Progenitor Cells as Potential Biomarker of Specific Acute Myeloid Leukemia Subtypes

et al. 2015

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MicroRNAs (miRNAs) are important regulators of several cellular processes. During hematopoiesis, specific expression signatures have been reported in different blood cell lineages and stages of hematopoietic stem cell (HSC) differentiation. Here we explored the expression of miRNAs in umbilical cord blood stem (HSC) and progenitor cells (HPC) and compared it to unilineage granulocyte and granulo-monocyte differentiation as well as to primary blasts from patients with acute myeloid leukemia (AML). CD34 + CD38- ad CD34 + CD38 + cells were profiled using a global array consisting of about 2000 miRNAs. An approach combining bioinformatic prediction of miRNA targets with mRNA expression profiling was used to search for putative biologically enriched functions and networks. At least 15 miRNAs to be differentially expressed between HSC and HPC cell population, a cluster of 7 miRNAs are located in the q32 region of human chromosome 14 (miR-377-3p, -136-5p, 376a-3p, 495-3p, 654-3p, 376c-3p and 381-3p) whose expression decreased during the early stages of normal myelopoiesis but were markedly increased in a small set of AML. Interestingly, miR-4739 and -4516, two novel microRNA whose function and targets are presently unknown, showed specific and peculiar expression profile during the hematopoietic stem cells differentiation into unilineages and resulted strongly upregulated in almost all AML subsets. miR-181, -126-5p, -29b-3p and -22-3p resulted dis-regulated in specific leukemias phenotypes. This study provides the first evidence of a miRNA signature in human cord blood stem and progenitor cells with a potential role in hematopoietic stemness properties and possibly in leukemogenesis of specific AML subtypes.

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“…It is noteworthy that recent evidence suggests that miRNAs exert a uniquely important role in cellular differentiation, development, proliferation and apoptosis [ 75 , 76 ]. Thus, it is not surprising that dysfunction of miRNAs in malignancies is involved in cancer pathogenesis [ 77 , 78 ], chemo/radiotherapy resistance [ 79 , 80 ], tumor metastasis [ 81 , 82 ], and other tumor-promoting mechanisms.…”

Section: Introductionmentioning

confidence: 99%

The microRNA feedback regulation of p63 in cancer progression

Lin

Zhang

et al. 2015

Oncotarget

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The transcription factor p63 is a member of the p53 gene family that plays a complex role in cancer due to its involvement in epithelial differentiation, cell cycle arrest and apoptosis. MicroRNAs are a class of small, non-coding RNAs with an important regulatory role in various cellular processes, as well as in the development and progression of cancer. A number of microRNAs have been shown to function as transcriptional targets of p63. Conversely, microRNAs also can modulate the expression and activity of p63. However, the p63–microRNA regulatory circuit has not been addressed in depth so far. Here, computational genomic analysis was performed using miRtarBase, Targetscan, microRNA.ORG, DIANA-MICROT, RNA22-HSA and miRDB to analyze miRNA binding to the 3′UTR of p63. JASPAR (profile score threshold 80%) and TFSEARCH datasets were used to search transcriptional start sites for p53/p63 response elements. Remarkably, these data revealed 63 microRNAs that targeted p63. Furthermore, there were 39 microRNAs targeting p63 that were predicted to be regulated by p63. These analyses suggest a crosstalk between p63 and microRNAs. Here, we discuss the crosstalk between p63 and the microRNA network, and the role of their interactions in cancer.

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MicroRNAs in the pathogenesis of myelodysplastic syndromes and myeloid leukaemia

Cited by 13 publications

References 58 publications

miR-194-5p/BCLAF1 deregulation in AML tumorigenesis

miR-194-5p/BCLAF1 deregulation in AML tumorigenesis

A miRNA Signature in Human Cord Blood Stem and Progenitor Cells as Potential Biomarker of Specific Acute Myeloid Leukemia Subtypes

The microRNA feedback regulation of p63 in cancer progression

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