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miR-486 is involved in the pathogenesis of acute myeloid leukemia by regulating JAK-STAT signaling

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Abstract

Acute myeloid leukemia (AML) is a widely prevalent disease worldwide and poses a large threat to public health. Previous studies have shown that AML is associated with cytogenetic heterogeneity, complex subtypes, and different therapeutic approaches. In this study, we found that miR-486 was upregulated in AML using both The Cancer Genome Atlas (TCGA) database and patient tissues. After knockdown of miR-486 by short hairpin RNA (shRNA), we discovered that miR-486 was required for cell proliferation. Through miRNA profile analysis and a dual-luciferase reporter assay, suppressor of cytokine signaling 2 (SOCS2) was identified as a direct target of miR-486. Therefore, by silencing SOCS2, a negative regulator of the Janus kinase (JAK)–signal transducer and activator of transcription (STAT) pathway, miR-486 enhanced JAK-STAT3 activity and promoted cell proliferation. The miR-486-SOCS2-STAT3 proliferation axis is therefore involved in the pathogenesis of AML, providing a novel molecular mechanism and diagnostic and therapeutic clues for AML.

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Authors and Affiliations

  1. Department of Oncology, The First People’s Hospital of Lianyungang, No. 6 Zhenhua Earth Road, Lianyungang City, 222061, Jiangsu Province, People’s Republic of China

    Cao Sha, Gao Jia, Zhao Jingjing, Hu Yapeng, Lou Zhi & Xu Guanghui

Authors
  1. Cao Sha
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  2. Gao Jia
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  3. Zhao Jingjing
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  4. Hu Yapeng
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  5. Lou Zhi
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  6. Xu Guanghui
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Contributions

Xu Guanghui designed the research and wrote the paper; Cao Sha, Zhao Jingjing, Gao Jia, and Hu Yapeng performed the research and analyzed the data. All authors read and approved the manuscript.

Corresponding author

Correspondence to Xu Guanghui.

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All data were generated in-house, and the authors did not use a paper mill.

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The authors declare that they have no competing interests.

Ethical standards

Patients were diagnosed according to the criteria of the World Health Organization classification of hematological malignancies. Before the initiation of treatment, clinical features, including Mantle Cell Lymphoma International Prognostic Index (MIPI) score, lactate dehydrogenase (LDH) content in serum, performance status (determined using Eastern Cooperative Oncology Group performance status scores), and white blood cell (WBC) counts, were collected. All experimental protocols and procedures involved in the present study were approved by the Ethics Committee of the First People’s Hospital of Lianyungang. Written informed consent was obtained from all participants prior to publication of this article.

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Sha, C., Jia, G., Jingjing, Z. et al. miR-486 is involved in the pathogenesis of acute myeloid leukemia by regulating JAK-STAT signaling. Naunyn-Schmiedeberg's Arch Pharmacol 394, 177–187 (2021). https://doi.org/10.1007/s00210-020-01892-4

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