miRNAs In Leukemia Research Articles

MicroRNAs in Leukemias: A Clinically Annotated Compendium

Leukemias are a group of malignancies of the blood and bone marrow. Multiple types of leukemia are known, however reliable treatments have not been developed for most leukemia types. Furthermore, even relatively reliable treatments can result in relapses. MicroRNAs (miRNAs) are a class of short, noncoding RNAs responsible for epigenetic regulation of gene expression and have been proposed as a source of potential novel therapeutic targets for leukemias. In order to identify central miRNAs for leukemia, we conducted data synthesis using two databases: miRTarBase and DISNOR. A total of 137 unique miRNAs associated with 16 types of leukemia were retrieved from miRTarBase and 86 protein-coding genes associated with leukemia were retrieved from the DISNOR database. Based on these data, we formed a visual network of 248 miRNA-target interactions (MTI) between leukemia-associated genes and miRNAs associated with ≥4 leukemia types. We then manually reviewed the literature describing these 248 MTIs for interactions identified in leukemia studies. This manually curated data was then used to visualize a network of 64 MTIs identified in leukemia patients, cell lines and animal models. We also formed a visual network of miRNA-leukemia associations. Finally, we compiled leukemia clinical trials from the ClinicalTrials database. miRNAs with the highest number of MTIs were miR-125b-5p, miR-155-5p, miR-181a-5p and miR-19a-3p, while target genes with the highest number of MTIs were TP53, BCL2, KIT, ATM, RUNX1 and ABL1. The analysis of 248 MTIs revealed a large, highly interconnected network. Additionally, a large MTI subnetwork was present in the network visualized from manually reviewed data. The interconnectedness of the MTI subnetwork suggests that certain miRNAs represent central disease molecules for multiple leukemia types. Additional studies on miRNAs, their target genes and associated biological pathways are required to elucidate the therapeutic potential of miRNAs in leukemia.

Characterization of microRNA expression profiles by deep sequencing of small RNA libraries in leukemia patients from Naxi ethnic

Background: Leukemia is a hematological malignancy characterized by the proliferation of early lymphoid precursors that replaces normal hematopoietic cells of the bone marrow. Nakhi (Naxi) ethnic minorities considered to be an area of low incidence. MicroRNAs (miRNAs) are a class of small noncoding RNAs that regulate the expression of other genes in various biological processes. The purpose of this work is to study the molecular mechanism of miRNAs in the leukemia from Naxi. Methods: Six leukemia patients (case 2 to case 7) and one healthy person (case 1) from Nakhi (Naxi) ethnic minorities were recruited. Total RNA was extracted from these samples and small RNA deep sequencing was performed. Results: A list of miRNAs (1,392 known and candidate 125 novels) expressed in leukocytes were identified, and many differentially regulated targets involved in several cellular pathways, such as cancer, Rap1 signaling pathway, Ras signaling pathway, and endocytosis. Additionally, quantitative real time-polymerase chain reaction (qRT-PCR) results show that hsa-miR-181b-5p, hsa-miR-181a-3p, hsa-miR-181a-5p, and hsa-miR-342-3p has different expression patterns in different cancer cells, hsa-miR-450a-5p, and hsa-miR-1255a were dysregulated in all leukemia cells. Conclusions: Several abnormal expressed miRNAs in leukemia patients were identified, the correlation of miRNAs dysregulation and leukemia biology demonstrates that specific miRNA can be potential therapeutic target.

MicroRNAs as biomarkers in leukemia.

Current diagnostic and prognostic markers still exhibit biological limitation and seeking novel molecular biomarkers is crucial for early clinical diagnosis and in the development of novel strategies for leukemia therapy. Emerging evidence showed that dysregulated microRNAs (miRNAs) play important roles in cancer including leukemia. In this review, we summarized recent progress on the role of miRNAs in leukemia, mainly focusing on recent findings that suggest the potential of miRNAs as biomarkers for diagnosis and prognosis. Notably, the circulating miRNAs were also discussed for the fact that they can be detected in body fluids, and thus represent a novel source of promising biomarkers that may be applied to clinical settings.

MicroRNAs in acute leukemia: from biological players to clinical contributors

MicroRNAs (miRNAs) are involved in the management of hematopoiesis. As a consequence, miRNA dysregulation causes disruption of the hematopoietic system and leukemia may arise. We here comprehensively discuss miRNAs found discriminative for cytogenetic and molecular subtypes of acute leukemia. These miRNAs are either known miRNAs involved in leukemogenesis with proven tumor suppressor or oncogenic activities or are newly identified by high-throughput sequencing with yet unknown function. Furthermore, forces are outlined that drive aberrant miRNA function, which include genetic abnormalities (for example, deletions, translocations and mutations) and epigenetic aberrations (for example, aberrant DNA methylation or histone modifications). Interestingly, leukemia-silenced miRNAs can be re-expressed upon treatment with de-methylating agents. Targeting miRNA expression may serve a therapeutical role, albeit at present this way of targeted therapy is in its infancy. However, emerging knowledge about the biology of miRNAs in leukemia may result into a role for these miRNAs in the diagnosis and treatment of acute leukemia.

Advance in the role of MicroRNAs in leukemia

MicroRNAs(miRNAs)are a series of short non-coding RNAs that can regulate the expressions of protein-coding genes posttranscriptionally.They modulate gene expression by targeting mRNA for degradation or blocking translation via base-pairing to complementary sites in the 3'-untranslated region of the target mRNAs.Their functions are related to many biology progresses and diseases including tumor and hematopoietic differentiation.They are speculated to be critical in the development, progression and prognosis of leukemia. In this review, we will summarize the research progress on miRNAs in leukemia. Key words: MicroRNAs; Leukemia; Regulation

New insight into the role of miRNAs in leukemia

Recent studies have shown that microRNAs(miRNAs) play an important role in cell differentiation, growth, and death, including the functional study of miRNAs in tumorigenesis. To date, miRNA expression profiles in many types of cancers have been identified and miRNA expression signatures associated with types and cytogenetics of leukemia have also been reported. Increasing evidence has shown that miRNAs could function as either tumor suppressors or oncogenes in cancers such as leukemia, while other miRNAs might be benefitcial for diagnosis and prognosis, predicted to be newly developed biomarkers. In this review, we summarize the recent progress about miRNAs in leukemia and present a miRNA-mediated network involved in differentiation, proliferation and apoptosis predicted to be the roles of miRNAs in the pathogenesis of leukemia.