Imbalanced expression of polycistronic miRNA in acute myeloid leukemia

Kotaki, Ryutaro; Handa, Hiroshi; Ogiya, Daisuke; Katahira, Yasuhiro; Kurosaki, Natsumi; Yukihira, Naoko; Ogata, Jun; Yamamoto, Haruna; Alba, Syakira Mohamad; Azhim, Azran; Kitajima, Tatsuo; Inoue, Shigeaki; Morishita, Kazuhiro; Ono, Koh; Koyama‐Nasu, Ryo; Kotani, Ai

doi:10.1007/s12185-017-2314-1

Cited by 4 publications

(4 citation statements)

References 23 publications

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“…miR-181a downregulated various phosphatases modulating sensitivity of T cells to antigen peptides, and overexpression of miR-181a in hematopoietic stem/progenitor cells increased fraction of B-lineage cells 6 , 7 . In line with these studies, we have found several miRNAs which can modulate hematopoiesis and can improve hematologic malignancy 8 – 11 .…”

Section: Introductionsupporting

confidence: 78%

Overexpression of miR-669m inhibits erythroblast differentiation

Kotaki

Kawashima

Yamaguchi

et al. 2020

Sci Rep

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MicroRNAs (miRNAs), one of small non-coding RNAs, regulate many cell functions through their post-transcriptionally downregulation of target genes. Accumulated studies have revealed that miRNAs are involved in hematopoiesis. In the present study, we investigated effects of miR-669m overexpression on hematopoiesis in mouse in vivo, and found that erythroid differentiation was inhibited by the overexpression. Our bioinformatic analyses showed that candidate targets of miR-669m which are involved in the erythropoiesis inhibition are A-kinase anchoring protein 7 (Akap7) and X-linked Kx blood group (Xk) genes. These two genes were predicted as targets of miR-669m by two different in silico methods and were upregulated in late erythroblasts in a public RNA-seq data, which was confirmed with qPCR. Further, miR-669m suppressed luciferase reporters for 3′ untranslated regions of Akap7 and Xk genes, which supports these genes are direct targets of miR-669m. Physiologically, miR-669m was not expressed in the erythroblast. In conclusion, using miR-669m, we found Akap7 and Xk, which may be involved in erythroid differentiation, implying that manipulating these genes could be a therapeutic way for diseases associated with erythropoiesis dysfunction.

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Section: Introductionsupporting

confidence: 78%

Overexpression of miR-669m inhibits erythroblast differentiation

Kotaki

Kawashima

Yamaguchi

et al. 2020

Sci Rep

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“…Some findings have extended our understanding of the uniqueness of KSHV gene regulation and provide valuable resources for the study of other genomic processes. The balance of polycistronic microRNA is regulated in a hierarchical manner after transcription, which may involve ecotropic virus integration site 1 (EVI1) [29]. The variations in organization of miRNA genes which acts as polycistronic transcripts clarify a multifunctional mechanism that controls gene expression in different biological processes [13].…”

Section: The Unique Polycistronic Structure Of the Mir-17-92 Clustermentioning

confidence: 99%

The MicroRNA Family Both in Normal Development and in Different Diseases: The miR-17-92 Cluster

Bai

Hua

Zhang

et al. 2019

BioMed Research International

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An increasing number of research studies over recent years have focused on the function of microRNA (miRNA) molecules which have unique characteristics in terms of structure and function. They represent a class of endogenous noncoding single-strand small molecules. An abundance of miRNA clusters has been found in the genomes of various organisms often located in a polycistron. The miR-17-92 family is among the most famous miRNAs and has been identified as an oncogene. The functions of this cluster, together with the seven individual molecules that it comprises, are most related to cancers, so it would not be surprising that they are considered to have involvement in the development of tumors. The miR-17-92 cluster is therefore expected not only to be a tumor marker, but also to perform an important role in the early diagnosis of those diseases and possibly also be a target for tumor biotherapy. The miR-17-92 cluster affects the development of disease by regulating many related cellular processes and multiple target genes. Interestingly, it also has important roles that cannot be ignored in disease of the nervous system and circulation and modulates the growth and development of bone. Therefore, it provides new opportunities for disease prevention, clinical diagnosis, prognosis, and targeted therapy. Here we review the role of the miR-17-92 cluster that has received little attention in relation to neurological diseases, cardiac diseases, and the development of bone and tumors.

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“…65 We previously found a link between miRNAs and hematological malignancies, and demonstrated that miRNAs are involved in cell differentiation and tumor progression. 66 - 69 In the next section, we discuss the role of exosome-mediated transfer of miRNAs in the development of lymphoid malignancy based on our findings.…”

Section: Exosomesmentioning

confidence: 98%

Significance of trogocytosis and exosome-mediated transport in establishing and maintaining the tumor microenvironment in lymphoid malignancies

Kawashima

Handa

Kotani

2021

JCEH

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The tumor immune microenvironment has been focused on in both solid and hematological tumors. Bystander cells in lymphoid malignancy are important for the progression of tumors. 1 Immune cells around the tumor contribute to the pro-tumor immunity, and support the survival and progression of the tumor as a niche. Immune cells are currently targeted for immunotherapy, for example, chimeric antigen receptor (CAR) -T cell therapy, 2 and immune checkpoint inhibitors such as anti-programmed cell death 1 (PD-1) antibody. 3 CAR-T cell therapy is particularly effective against hematological tumors. In the case of classic Hodgkin lymphoma (cHL), anti-PD-1 antibody is highly effective. This suggests that the immune interactions between the tumor and its surrounding cells are important for the progression of hematological tumors and their therapy.Intercellular communication tools, such as cytokines and chemokines, are important for educating tumor biology. Furthermore, intercellular transfer of molecules, such as via trogocytosis and exosomes, was recently reported to be involved in facilitating the interaction between the tumor and surrounding immune cells. [4][5][6][7] Although cytokines and chemokines induce gene expression of target cells, they must undergo signal transduction. Trogocytosis and exosomes mediate direct transfer of molecules from donor cells to target cells. 8 They may be able to control the function of target cells more rapidly than the induction of gene expression by cytokines and chemokines.In this article, we reviewed these biological phenomena functioning in lymphoid malignancy based on our findings. TROGOCYTOSISTrogocytosis is a phenomenon characterized by the directional movement of molecules between the interacting cells or towards the cells connected to a donor cell via the interchanging junctions of the plasma membrane. 9,10 In the 1970s, the proteins that were specifically expressed in one cell type were detected from the surface of other cell types. 11,12 The transfer of major histocompatibility complex (MHC) molecule from antigen-presenting cells (APCs) to

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Imbalanced expression of polycistronic miRNA in acute myeloid leukemia

Cited by 4 publications

References 23 publications

Overexpression of miR-669m inhibits erythroblast differentiation

Overexpression of miR-669m inhibits erythroblast differentiation

The MicroRNA Family Both in Normal Development and in Different Diseases: The miR-17-92 Cluster

Significance of trogocytosis and exosome-mediated transport in establishing and maintaining the tumor microenvironment in lymphoid malignancies

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