scholarly journals Distinct noncoding RNAs and RNA binding proteins associated with high‐risk pediatric and adult acute myeloid leukemia s detected by regulatory network analysis

2021 ◽  
Author(s):  
Zhenqiu Liu ◽  
Vladimir S. Spiegelman ◽  
Hong‐Gang Wang
Keyword(s):  
Acute Myeloid Leukemia ◽  
High Risk ◽  
Network Analysis ◽  
Regulatory Network ◽  
Myeloid Leukemia ◽  
Binding Proteins ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Noncoding Rnas ◽  
Acute Myeloid

scholarly journals Small-molecule targeting of MUSASHI RNA-binding activity in acute myeloid leukemia

2018 ◽  
Author(s):  
Gerard Minuesa ◽  
Steven K. Albanese ◽  
Arthur Chow ◽  
Alexandra Schurer ◽  
Sun-Mi Park ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Small Molecule ◽  
Myeloid Leukemia ◽  
Binding Proteins ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Wide Spectrum ◽  
Gene Expression Signature ◽  
Acute Myeloid

SUMMARYThe MUSASHI family of RNA binding proteins (MSI1 and MSI2) contribute to a wide spectrum of cancers including acute myeloid leukemia. We found that the small molecule Ro 08–2750 (Ro) directly binds to MSI2 and competes for its RNA binding in biochemical assays. Ro treatment in mouse and human myeloid leukemia cells resulted in an increase in differentiation and apoptosis, inhibition of known MSI-targets, and a shared global gene expression signature similar to shRNA depletion of MSI2. Ro demonstrated in vivo inhibition of c-MYC and reduced disease burden in a murine AML leukemia model. Thus, we have identified a small molecule that targets MSI’s oncogenic activity. Our study provides a framework for targeting RNA binding proteins in cancer.

scholarly journals Expression, Regulation and Function of microRNA as Important Players in the Transition of MDS to Secondary AML and Their Cross Talk to RNA-Binding Proteins

2020 ◽  
Vol 21 (19) ◽  
pp. 7140 ◽  
Author(s):  
Marcus Bauer ◽  
Christoforos Vaxevanis ◽  
Nadine Heimer ◽  
Haifa Kathrin Al-Ali ◽  
Nadja Jaekel ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Binding Proteins ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Significant Risk ◽  
Control Of Gene Expression ◽  
Hematopoietic Stem ◽  
Molecular Abnormalities ◽  
Acute Myeloid

Myelodysplastic syndromes (MDS), heterogeneous diseases of hematopoietic stem cells, exhibit a significant risk of progression to secondary acute myeloid leukemia (sAML) that are typically accompanied by MDS-related changes and therefore significantly differ to de novo acute myeloid leukemia (AML). Within these disorders, the spectrum of cytogenetic alterations and oncogenic mutations, the extent of a predisposing defective osteohematopoietic niche, and the irregularity of the tumor microenvironment is highly diverse. However, the exact underlying pathophysiological mechanisms resulting in hematopoietic failure in patients with MDS and sAML remain elusive. There is recent evidence that the post-transcriptional control of gene expression mediated by microRNAs (miRNAs), long noncoding RNAs, and/or RNA-binding proteins (RBPs) are key components in the pathogenic events of both diseases. In addition, an interplay between RBPs and miRNAs has been postulated in MDS and sAML. Although a plethora of miRNAs is aberrantly expressed in MDS and sAML, their expression pattern significantly depends on the cell type and on the molecular make-up of the sample, including chromosomal alterations and single nucleotide polymorphisms, which also reflects their role in disease progression and prediction. Decreased expression levels of miRNAs or RBPs preventing the maturation or inhibiting translation of genes involved in pathogenesis of both diseases were found. Therefore, this review will summarize the current knowledge regarding the heterogeneity of expression, function, and clinical relevance of miRNAs, its link to molecular abnormalities in MDS and sAML with specific focus on the interplay with RBPs, and the current treatment options. This information might improve the use of miRNAs and/or RBPs as prognostic markers and therapeutic targets for both malignancies.

scholarly journals Assessment of The Lnc-CCAT1/miR-155a Regulatory Network in Acute Myeloid Leukemia

2019 ◽  
pp. 1-8
Author(s):  
Nashwa EL-Khazragy ◽  
Magdy Mohamed ◽  
Rehab Abdelmaksoud ◽  
Eman Saleh
Keyword(s):  
Acute Myeloid Leukemia ◽  
High Risk ◽  
Regulatory Network ◽  
Myeloid Leukemia ◽  
Noncoding Rna ◽  
Prognostic Biomarker ◽  
Clinical Samples ◽  
Monocytic Differentiation ◽  
High Risk Factors ◽  
Acute Myeloid

Colon cancer-associated transcript_1 (CCAT1) is a long noncoding RNA that maps to chromosome 8q24.21, it was first discovered to be upregulated in colorectal cancer. Recent studies have observed the CCAT1 overexpression in primary human solid cancers and cell lines as well as in AML, moreover, it repressed monocytic differentiation and promoted cell growth of HL-60 by sequestering tumor suppressive miR-155. However, the prognostic value of CCAT1/miR-155a pathway in acute myeloid Leukemia (AML) has not been investigated on clinical samples. In this study, the expression levels of CCAT1 and miR_155a was measured in 150 AML patients with standard and high-risk factors; CCAT1 and miR_155a were increased by 2.7 and 5.7 folds; respectively in AML compared to healthy controls. Furtherly, upregulation of both biomarkers was significantly associated with high risk AML. Collectively, these results suggest that CCAT1 and miR_155a can be considered as a diagnostic and prognostic biomarker in AML.

PlncRNADB: A Repository of Plant lncRNAs and lncRNA-RBP Protein Interactions

2019 ◽  
Vol 14 (7) ◽  
pp. 621-627 ◽  
Author(s):  
Youhuang Bai ◽  
Xiaozhuan Dai ◽  
Tiantian Ye ◽  
Peijing Zhang ◽  
Xu Yan ◽  
...  
Keyword(s):  
Protein Interactions ◽  
Binding Proteins ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Populus Trichocarpa ◽  
Noncoding Rnas ◽  
Reference Database ◽  
Protein Coding ◽  
Arabidopsis Lyrata ◽  
User Friendly

Background: Long noncoding RNAs (lncRNAs) are endogenous noncoding RNAs, arbitrarily longer than 200 nucleotides, that play critical roles in diverse biological processes. LncRNAs exist in different genomes ranging from animals to plants. Objective: PlncRNADB is a searchable database of lncRNA sequences and annotation in plants. Methods: We built a pipeline for lncRNA prediction in plants, providing a convenient utility for users to quickly distinguish potential noncoding RNAs from protein-coding transcripts. Results: More than five thousand lncRNAs are collected from four plant species (Arabidopsis thaliana, Arabidopsis lyrata, Populus trichocarpa and Zea mays) in PlncRNADB. Moreover, our database provides the relationship between lncRNAs and various RNA-binding proteins (RBPs), which can be displayed through a user-friendly web interface. Conclusion: PlncRNADB can serve as a reference database to investigate the lncRNAs and their interaction with RNA-binding proteins in plants. The PlncRNADB is freely available at http://bis.zju.edu.cn/PlncRNADB/.

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