The transcription factor TAL1 and miR-17-92 create a regulatory loop in hematopoiesis

Meyer, Annekarin; Herkt, Stefanie; Kunze‐Schumacher, Heike; Kohrs, Nicole; Ringleb, Julia; Schneider, Lucas; Kuvardina, Olga N.; Oellerich, Thomas; Häupl, Björn; Krueger, Andreas; Seifried, Erhard; Bönig, Halvard; Lausen, Joern

doi:10.1038/s41598-020-78629-z

Cited by 11 publications

(8 citation statements)

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“…The most significant enrichment was of targets for E47, an activator of adiponectin expression (Doran et al, 2008). E47 regulates hematopoiesis, and its expression in blood cells could therefore determine to establish obesity-related lineages (Meyer et al, 2020). Other relevant target enrichments were for RREB1, which is also encoded by an Ow-dmCpGhosting gene, and for SREBP1, a partner of E47 in adiponectin expression activation and an extensively studied regulator of FA metabolism (Doran et al, 2008;Jump, 2011).…”

Section: Discussionmentioning

confidence: 99%

Distinct Associations of BMI and Fatty Acids With DNA Methylation in Fasting and Postprandial States in Men

et al. 2021

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We have previously shown that blood global DNA methylation (DNAm) differs between postprandial state (PS) and fasting state (FS) and is associated with BMI and polyunsaturated fatty acid (PUFA) (negatively and positively, respectively) in 12 metabolically healthy adult Mexican men (AMM cohort) equally distributed among conventional BMI classes. Here, we detailed those associations at CpG dinucleotide level by exploiting the Infinium methylation EPIC array (Illumina). We sought differentially methylated CpG (dmCpG) that were (1) associated with BMI (BMI-dmCpG) and/or fatty acids (FA) (FA-dmCpG) in FS or PS and (2) different across FS and PS within a BMI class. BMI-dmCpG and FA-dmCpG were more numerous in FS compared to PS and largely prandial state-specific. For saturated and monounsaturated FA, dmCpG overlap was higher across than within the respective saturation group. Several BMI- and FA-dmCpG mapped to genes involved in metabolic disease and in some cases matched published experimental data sets. Notably, SETDB1 and MTHFS promoter dmCpG could explain the previously observed associations between global DNAm, PUFA content, and BMI in FS. Surprisingly, overlap between BMI-dmCpG and FA-dmCpG was limited and the respective dmCpG were differentially distributed across functional genomic elements. BMI-dmCpG showed the highest overlap with dmCpG of the saturated FA palmitate, monounsaturated C20:1 and PUFA C20:2. Of these, selected promoter BMI-dmCpG showed opposite associations with palmitate compared to C20:1 and C20:2. As for the comparison between FS and PS within BMI classes, dmCpG were strikingly more abundant and variably methylated in overweight relative to normoweight or obese subjects (∼70–139-fold, respectively). Overweight-associated dmCpG-hosting genes were significantly enriched in targets for E47, SREBP1, and RREB1 transcription factors, which are known players in obesity and lipid homeostasis, but none overlapped with BMI-dmCpG. We show for the first time that the association of BMI and FA with methylation of disease-related genes is distinct in FS and PS and that limited overlap exists between BMI- and FA-dmCpG within and across prandial states. Our study also identifies a transcriptional regulation circuitry in overweight that might contribute to adaptation to that condition or to transition to obesity. Further work is necessary to define the pathophysiological implications of these findings.

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Section: Discussionmentioning

confidence: 99%

Distinct Associations of BMI and Fatty Acids With DNA Methylation in Fasting and Postprandial States in Men

et al. 2021

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“…showed that reduced expression of miR-92 promotes proliferation, migration, invasion and apoptosis in GBM cells by targeting neogenin (NEO1) ( 41 ). In addition, miR-92b transcription is regulated by transcription factors like TAL1-E47 during hematopoiesis and embryogenesis, SP1 during cell differentiation and apoptosis, and HiF1 during hypoxic conditions ( 42 – 44 ). In our study, we performed a rigorous bioinformatics analysis combined with real-time PCR, and western blots to identify potential miR-92b target genes.…”

Section: Discussionmentioning

confidence: 99%

MicroRNA-92b targets tumor suppressor gene FBXW7 in glioblastoma

Grafals-Ruiz,

Sánchez-Álvarez,

Santana-Rivera

et al. 2023

Front. Oncol.

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IntroductionGlioblastoma (GBM) is a highly aggressive and lethal primary brain tumor. Despite limited treatment options, the overall survival of GBM patients has shown minimal improvement over the past two decades. Factors such as delayed cancer diagnosis, tumor heterogeneity, cancer stem cell survival, infiltrative nature of GBM cells, metabolic reprogramming, and development of therapy resistance contribute to treatment failure. To address these challenges, multitargeted therapies are urgently needed for improved GBM treatment outcomes. MicroRNAs (miRNAs) are small non-coding RNAs that regulate gene expression. Dysregulated miRNAs have been identified in GBM, playing roles in tumor initiation, progression, and maintenance. Among these miRNAs, miR-92b (miRNA-92b-3p) has been found to be overexpressed in various cancers, including GBM. However, the specific target genes of miR-92b and its therapeutic potential in GBM remain poorly explored.MethodsSamples encompassed T98G, U87, and A172 human GBM cell lines, GBM tumors from Puerto Rican patients, and murine tumors. In-situ hybridization (ISH) assessed miR-92b expression in patient tumors. Transient and stable transfections modified miR-92b levels in GBM cell lines. Real-time PCR gauged gene expressions. Caspase 3 and Trypan Blue assays evaluated apoptosis and viability. Bioinformatics tools (TargetScanHuman 8.0, miRDB, Diana tools, miRWalk) predicted targets. Luciferase assays and Western Blots validated miRNA-target interactions. A subcutaneous GBM Xenograft mouse model received intraperitoneal NC-OMIs or miR92b-OMIs encapsulated in liposomes, three-times per week for two weeks. Analysis utilized GraphPad Prism 8; statistical significance was assessed using 2-tailed, unpaired Student’s t-test and two-way ANOVA as required.ResultsThis study investigated the expression of miR-92b in GBM tumors compared to normal brain tissue samples, revealing a significant upregulation. Inhibition of miR-92b using oligonucleotide microRNA inhibitors (OMIs) suppressed GBM cell growth, migration, and induced apoptosis, while ectopic expression of miR-92b yielded opposite effects. Systemic administration of liposomal-miR92b-OMIs in GBM xenograft mice resulted in reductions in tumor volume and weight. Subsequent experiments identified F-Box and WD Repeat Domain Containing 7 (FBXW7) as a direct target gene of miR-92b in GBM cells.DiscussionFBXW7 acts as a tumor suppressor gene in various cancer types, and analysis of patient data demonstrated that GBM patients with higher FBXW7 mRNA levels had significantly better overall survival compared to those with lower levels. Taken together, our findings suggest that the dysregulated expression of miR-92b in GBM contributes to tumor progression by targeting FBXW7. These results highlight the potential of miR-92b as a therapeutic target for GBM. Further exploration and development of miR-92b-targeted therapies may offer a novel approach to improve treatment outcomes in GBM patients.

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“…The miR-17–92 cluster expression decreases during terminal erythroid differentiation, and its overexpression by targeting TAL1 negatively affects erythroid lineage differentiation [ 92 ].…”

Section: Mirna Regulation In Erythropoiesis (Table 2 ...mentioning

confidence: 99%

Insight into microRNAs’ involvement in hematopoiesis: current standing point of findings

Nassiri,

Ahmadi Afshar,

Almasi

2023

Stem Cell Res Ther

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Hematopoiesis is a complex process in which hematopoietic stem cells are differentiated into all mature blood cells (red blood cells, white blood cells, and platelets). Different microRNAs (miRNAs) involve in several steps of this process. Indeed, miRNAs are small single-stranded non-coding RNA molecules, which control gene expression by translational inhibition and mRNA destabilization. Previous studies have revealed that increased or decreased expression of some of these miRNAs by targeting several proto-oncogenes could inhibit or stimulate the myeloid and erythroid lineage commitment, proliferation, and differentiation. During the last decades, the development of molecular and bioinformatics techniques has led to a comprehensive understanding of the role of various miRNAs in hematopoiesis. The critical roles of miRNAs in cell processes such as the cell cycle, apoptosis, and differentiation have been confirmed as well. However, the main contribution of some miRNAs is still unclear. Therefore, it seems undeniable that future studies are required to focus on miRNA activities during various hematopoietic stages and hematological malignancy.

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The transcription factor TAL1 and miR-17-92 create a regulatory loop in hematopoiesis

Cited by 11 publications

References 75 publications

Distinct Associations of BMI and Fatty Acids With DNA Methylation in Fasting and Postprandial States in Men

Distinct Associations of BMI and Fatty Acids With DNA Methylation in Fasting and Postprandial States in Men

MicroRNA-92b targets tumor suppressor gene FBXW7 in glioblastoma

Insight into microRNAs’ involvement in hematopoiesis: current standing point of findings

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