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Abstract
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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1 Tokai University, Department of Hematological Malignancy, Institute of Medical Science, Isehara, Japan (GRID:grid.265061.6) (ISNI:0000 0001 1516 6626)
2 Tokai University, Department of Hematological Malignancy, Institute of Medical Science, Isehara, Japan (GRID:grid.265061.6) (ISNI:0000 0001 1516 6626); The Jikei University School of Medicine, Division of Clinical Oncology and Hematology, Tokyo, Japan (GRID:grid.411898.d) (ISNI:0000 0001 0661 2073)
3 Tokai University, Department of Hematological Malignancy, Institute of Medical Science, Isehara, Japan (GRID:grid.265061.6) (ISNI:0000 0001 1516 6626); Kitasato University, Department of Biosciences, School of Science, Sagamihara, Japan (GRID:grid.410786.c) (ISNI:0000 0000 9206 2938)
4 Tokai University, Department of Hematological Malignancy, Institute of Medical Science, Isehara, Japan (GRID:grid.265061.6) (ISNI:0000 0001 1516 6626); Kitasato University, Department of Biosciences, School of Science, Sagamihara, Japan (GRID:grid.410786.c) (ISNI:0000 0000 9206 2938); The University of Tokyo, Department of Computational Biology and Medical Sciences, Graduate School of Frontier Sciences, Kashiwa, Japan (GRID:grid.26999.3d) (ISNI:0000 0001 2151 536X)
5 Tokai University School of Medicine, Department of Hematology and Oncology, Isehara, Japan (GRID:grid.265061.6) (ISNI:0000 0001 1516 6626)
6 Tottori University, Division of Immunology, Department of Molecular and Cellular Biology, School of Life Science, Faculty of Medicine, Yonago, Japan (GRID:grid.265107.7) (ISNI:0000 0001 0663 5064)
7 Tokai University School of Medicine, Department of Molecular Life Science, Division of Basic Medical Science and Molecular Medicine, Isehara, Japan (GRID:grid.265061.6) (ISNI:0000 0001 1516 6626)
8 Tokai University School of Medicine, Biomedical Informatics Laboratory, Department of Molecular Life Science, Isehara, Japan (GRID:grid.265061.6) (ISNI:0000 0001 1516 6626); Tokai University, Micro/Nano Technology Center, Hiratsuka, Japan (GRID:grid.265061.6) (ISNI:0000 0001 1516 6626)
9 Kitasato University, Department of Biosciences, School of Science, Sagamihara, Japan (GRID:grid.410786.c) (ISNI:0000 0000 9206 2938)
10 Tokai University, Department of Hematological Malignancy, Institute of Medical Science, Isehara, Japan (GRID:grid.265061.6) (ISNI:0000 0001 1516 6626); Japan Science and Technology Agency, Precursory Research for Embryonic Science and Technology, Saitama, Japan (GRID:grid.419082.6) (ISNI:0000 0004 1754 9200); AMED-PRIME, Japan Agency for Medical Research and Development, Tokyo, Japan (GRID:grid.480536.c) (ISNI:0000 0004 5373 4593)