MicroRNAs and response to therapy in leukemia

Mirzaei, Hossein; Abadi, Mohammad Hassan Jafari Najaf; Razi, Ebrahim; Mousavi, Nousin; Morovati, Hamid; Sarvizadeh, Mostafa; Taghizadeh, Mohsen

doi:10.1002/jcb.28892

Cited by 6 publications

(4 citation statements)

References 143 publications

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“…Several miRNAs have been studied for their diagnostic, prognostic or therapeutic potential [ 73 ]. Results of a meta-analysis of miR-155 and its role in overall survival of AML and CLL patients indicate that high miR-155 expression is associated with lower overall survival of patients, making it a promising prognostic biomarker [ 74 ].…”

Section: Discussionmentioning

confidence: 99%

MicroRNAs in Leukemias: A Clinically Annotated Compendium

Turk

Calin

Kunej

2022

IJMS

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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.

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Section: Discussionmentioning

confidence: 99%

MicroRNAs in Leukemias: A Clinically Annotated Compendium

Turk

Calin

Kunej

2022

IJMS

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“…Evidence has shown that miRNAs can participate in the occurrence and development of tumors as oncogenes or tumor suppressor genes. Recent years have seen an increase in research on the role of miRNA in the pathogenesis of leukemia [7][8][9] . miR-15a/16-1, miR-188, miR-155, miR-29, miR-17-92, and let-7 are the most commonly differentially expressed miRNAs reported in leukemia [10] .…”

Section: Discussionmentioning

confidence: 99%

Expression and Clinical Significance of miRNA-495 in the Peripheral Blood of Acute Myeloid Leukemia Patients

Huang

Dai

2022

PAR

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Objective: To analyze the expression and clinical significance of miRNA-495 in the peripheral blood of patients with acute myeloid leukemia. Methods: Fifty-six patients with acute myeloid leukemia and 56 healthy controls were selected. Fasting venous blood was drawn and centrifuged, and the plasma was collected. The target miRNA was directly amplified and reverse transcribed into cDNA. The expression of plasma miR-495 was detected by qRT-PCR. Results: The expression level of miRNA-495 in newly diagnosed acute myeloid leukemia (AML [ND]) and relapsed/refractory acute myeloid leukemia (AML [RR]) was significantly lower than that in complete remission (AML [CR]) and normal control group (Control) (p < 0.0001). There was no significant difference between AML (ND) group and AML (RR) group (p > 0.05). The area under the ROC curve (AUC) of miRNA-495 was 0.9503, the 95% confidence interval was 0.9113–0.9892 (p < 0.0001), the standard error was 0.020, the sensitivity and specificity were 91.1% and 92.9%, respectively, and the Jordan index was 0.857. There was no significant difference between the expression level of miRNA-495 and gender, age, leukocyte count, hemoglobin, and platelet count (p > 0.05). However, it was found related to the proportion of primitive bone marrow cells in patients (p = 0.017). Conclusion: The decreased expression of plasma miR-495 in AML patients can be used as a new indicator for the diagnosis and prognosis of AML.

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“…Manipulation of miR-101 is engaged by breast cancer cells to ensure higher proteasome activity along with higher proliferation rates [ 109 ]. miRNAs—including miR-101 and others—are associated with cancer immunity [ 110 ] and thus discussed as a potential therapeutic target. In this context, miR-101 is also proposed to target Jak2 [ 111 ].…”

Section: The Immunoproteasome: a Proteasomal Variant Linked To The Hematopoietic Systemmentioning

confidence: 99%

Immunoproteasome Function in Normal and Malignant Hematopoiesis

Tubío-Santamaría

Ebstein

Heidel

et al. 2021

Cells

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The ubiquitin–proteasome system (UPS) is a central part of protein homeostasis, degrading not only misfolded or oxidized proteins but also proteins with essential functions. The fact that a healthy hematopoietic system relies on the regulation of protein homeostasis and that alterations in the UPS can lead to malignant transformation makes the UPS an attractive therapeutic target for the treatment of hematologic malignancies. Herein, inhibitors of the proteasome, the last and most important component of the UPS enzymatic cascade, have been approved for the treatment of these malignancies. However, their use has been associated with side effects, drug resistance, and relapse. Inhibitors of the immunoproteasome, a proteasomal variant constitutively expressed in the cells of hematopoietic origin, could potentially overcome the encountered problems of non-selective proteasome inhibition. Immunoproteasome inhibitors have demonstrated their efficacy and safety against inflammatory and autoimmune diseases, even though their development for the treatment of hematologic malignancies is still in the early phases. Various immunoproteasome inhibitors have shown promising preliminary results in pre-clinical studies, and one inhibitor is currently being investigated in clinical trials for the treatment of multiple myeloma. Here, we will review data on immunoproteasome function and inhibition in hematopoietic cells and hematologic cancers.

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MicroRNAs and response to therapy in leukemia

Cited by 6 publications

References 143 publications

MicroRNAs in Leukemias: A Clinically Annotated Compendium

MicroRNAs in Leukemias: A Clinically Annotated Compendium

Expression and Clinical Significance of miRNA-495 in the Peripheral Blood of Acute Myeloid Leukemia Patients

Immunoproteasome Function in Normal and Malignant Hematopoiesis

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