Translation Regulation by microRNAs in Acute Leukemia

Kontos, Christos K.; Vasilatou, Diamantina; Papageorgiou, Sotirios; Scorilas, Andreas

doi:10.1002/3527600906.mcb.20130010

Cited by 5 publications

(5 citation statements)

References 121 publications

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“…Distinct 3'-untranslated regions (3'-UTRs) of splice variants of a single protein-coding gene resulting from alternative splicing may have other implications, including different regulatory properties. As microRNAs (miRNAs) bind 3'-UTRs to downregulate the levels of the respective proteins or protein isoforms, alterations in their sequence due to alternative splicing may account for the regulation of splice variants by distinct miRNAs (57). Thus, miRNAs regulating the expression of protein-coding transcripts subjected to intense alternative splicing may constitute very promising molecular biomarkers; such miRNAs include members of the miR-17/92 cluster (58) and its paralogue miR-106a/363, such as miR-92a-3p and miR-20b-5p as well as miR-155-5p, which have pivotal roles in other B-cell malignancies, including chronic lymphocytic leukemia (59)(60)(61).…”

Section: Biological and Clinical Significance Of Splice Variantsmentioning

confidence: 99%

Alternative Splicing Detection Tool—a novel PERL algorithm for sensitive detection of splicing events, based on next-generation sequencing data analysis

Adamopoulos¹,

Theodoropoulou²,

Scorilas³

2018

Ann. Transl. Med.

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Next-generation sequencing (NGS) can provide researchers with high impact information regarding alternative splice variants or transcript identifications. However, the enormous amount of data acquired from NGS platforms make the analysis of alternative splicing events hard to accomplish. For this reason, we designed the "Alternative Splicing Detection Tool" (ASDT), an algorithm that is capable of identifying alternative splicing events, including novel ones from high-throughput NGS data. ASDT is available as a PERL script at http://aias.biol.uoa.gr/~mtheo and can be executed on any system with PERL installed. In addition to the detection of annotated and novel alternative splicing events from high-throughput NGS data, ASDT can also analyze the intronic regions of genes, thus enabling the detection of novel cryptic exons residing in annotated introns, extensions of previously annotated exons, or even intron retentions. Consequently, ASDT demonstrates many innovative and unique features that can efficiently contribute to alternative splicing analysis of NGS data.

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Section: Biological and Clinical Significance Of Splice Variantsmentioning

confidence: 99%

Alternative Splicing Detection Tool—a novel PERL algorithm for sensitive detection of splicing events, based on next-generation sequencing data analysis

Adamopoulos¹,

Theodoropoulou²,

Scorilas³

2018

Ann. Transl. Med.

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“…Members of the miR-17/92 cluster and its paralogue miR-106a/363, such as miR-92a-3p and miR-20b-5p, along with miR-155-5p have pivotal roles in other B-cell malignancies, including chronic lymphocytic leukemia (36)(37)(38). In particular, miR-155-5p regulates important transcription factors, such as E2F2 and hypoxiainducible factor 1 (HIF1) in leukemic cells (39,40).…”

Section: Introductionmentioning

confidence: 99%

Non-coding RNAs: the riddle of the transcriptome and their perspectives in cancer

Diamantopoulos¹,

Tsiakanikas²,

Scorilas³

2018

Ann. Transl. Med.

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100

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Non-coding RNAs (ncRNAs) constitute a heterogeneous group of RNA molecules in terms of biogenesis, biological function as well as length and structure. These biological molecules have gained attention recently as a potentially crucial layer of tumor cell progression or regulation. ncRNAs are expressed in a broad spectrum of tumors, and they play an important role not only in maintaining but also in promoting cancer development and progression. Recent discoveries have revealed that ncRNAs may act as key signal transduction mediators in tumor signaling pathways by interacting with RNA or proteins. These results reinforce the hypothesis, that ncRNAs constitute therapeutic targets, and point out their clinical potential as stratification markers. The major purpose of this review is to mention the emergence of the importance of ncRNAs, as molecules which are correlated with cancer, and to discuss their clinical implicit as prognostic diagnostic indicators, biomarkers, and therapeutic targets.

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“…Dysregulation of their expression levels contributes significantly to the development and/or progression of many human diseases, including cancer and leukemias [ 31 ]. Several miRNAs have been suggested as promising therapeutic targets in the battle against leukemia, as restoration of their normal expression in leukemic cells can dramatically alter the expression levels of key proteins that are heavily involved in leukemia pathobiology [ 32 ]. Moreover, some of these small noncoding RNAs have prognostic value in particular hematological malignancies [ 32 ].…”

Section: Discussionmentioning

confidence: 99%

MicroRNA-155-5p Overexpression in Peripheral Blood Mononuclear Cells of Chronic Lymphocytic Leukemia Patients Is a Novel, Independent Molecular Biomarker of Poor Prognosis

et al. 2017

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MicroRNA-155-5p (miR-155-5p) is a proinflammatory, oncogenic miRNA, involved in various physiological processes, including hematopoiesis, immunity, inflammation, and cell lineage differentiation. It regulates important transcription factors, such as E2F2, hypoxia-inducible factor 1 (HIF1), and FOXO3. Recently, the dysregulation of miR-155-5p expression has been linked to chronic lymphocytic leukemia (CLL) pathogenesis. In this research study, we investigated the potential diagnostic and prognostic value of miR-155-5p in CLL. To achieve our goal, we isolated total RNA from peripheral blood mononuclear cells (PBMCs) collected from 88 CLL patients and 36 nonleukemic blood donors and performed polyadenylation of total RNA and reverse transcription. Next, we quantified miR-155-5p levels using an in-house-developed real-time quantitative PCR method, before proceeding to extensive biostatistical analysis. Thus, it appears that miR-155-5p is significantly overexpressed in PBMCs of CLL patients and can distinguish them from nonleukemic population. Kaplan-Meier OS analysis and bootstrap univariate Cox regression showed that high miR-155-5p expression predicts inferior OS for CLL patients (p < 0.001). Interestingly, miR-155-5p overexpression retains its unfavorable prognostic role in CLL patients stratified according to established prognostic factors [CD38 expression and mutational status of the immunoglobulin heavy chain variable region (IGHV)]. Thus, miR-155-5p appears as a promising, independent molecular biomarker of unfavorable prognosis in CLL.

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Translation Regulation by microRNAs in Acute Leukemia

Cited by 5 publications

References 121 publications

Alternative Splicing Detection Tool—a novel PERL algorithm for sensitive detection of splicing events, based on next-generation sequencing data analysis

Alternative Splicing Detection Tool—a novel PERL algorithm for sensitive detection of splicing events, based on next-generation sequencing data analysis

Non-coding RNAs: the riddle of the transcriptome and their perspectives in cancer

MicroRNA-155-5p Overexpression in Peripheral Blood Mononuclear Cells of Chronic Lymphocytic Leukemia Patients Is a Novel, Independent Molecular Biomarker of Poor Prognosis

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