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Oncogenes, Fusion Genes and Tumor Suppressor Genes

An oncogenic role of miR-142-3p in human T-cell acute lymphoblastic leukemia (T-ALL) by targeting glucocorticoid receptor-α and cAMP/PKA pathways

Leukemia volume 26, pages 769–777 (2012)Cite this article

Abstract

MicroRNAs (miRNAs) are a family of 19–24 nucleotide non-coding RNAs with posttranscriptional regulatory functions. The involvement of miRNAs in normal hematopoiesis implies that deregulated miRNAs might contribute to leukemogenesis. To date, although certain miRNAs have been established a clear oncogenic role in hematological malignancies, other individual miRNAs potentially involved in human leukemogenesis still remain elusive. In this report, we showed that miR-142-3p was upregulated in human T-leukemic cell lines and primary T-leukemic cells isolated from T-cell acute lymphoblastic leukemia (T-ALL) patients and its expressive levels were correlated with patients’ prognosis. Such an oncogenic role of miR-142-3p could be explained by its targeting cyclic adenosine monophosphate (cAMP)/protein kinase A (PKA) and glucocorticoid receptor alpha (GRα). High levels of miR-142-3p resulted in low levels of cAMP and weak activity of PKA, thus relieving the inhibitory effect of PKA on T-leukemic cell proliferation. Meanwhile, miR-142-3p decreased GRα protein expression by directly targeting the 3′-untranslational region of GRα mRNA, leading to glucocorticoid resistance. Transfection of the miR-142-3p inhibitor effectively converted glucocorticoid resistance, because of the resultant increase of GRα expression and PKA activity. These findings suggest that miR-142-3p is critical in T-cell leukemogenesis and may serve as a potential therapeutic target in T-ALL patients.

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Acknowledgements

We thank the patients for their cooperation and confidence. This study was supported by the Funds for International Cooperation and Exchange of the National Natural Science Foundation of China (30911120482), the National Science Foundation of China (30770911, 81070449), the Program for New Century Excellent Talents in University (NCET-08-0219) and the Beijing Natural Science Foundation (7112139).

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  1. M Lv and X Zhang: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Biochemistry and Molecular Biology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, The People's Republic of China

    M Lv, D Li, B Zhang, H Zhang & B Huang

  2. Peking University Institute of Hematology, Peking University People's Hospital, Peking University, Beijing, The People's Republic of China

    M Lv, X Zhang, Q Jiang, J Lu & X Huang

  3. Department of Biology Science, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, The People's Republic of China

    H Jia & T Jiang

  4. Department of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, The People's Republic of China

    M Hong

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Lv, M., Zhang, X., Jia, H. et al. An oncogenic role of miR-142-3p in human T-cell acute lymphoblastic leukemia (T-ALL) by targeting glucocorticoid receptor-α and cAMP/PKA pathways. Leukemia 26, 769–777 (2012). https://doi.org/10.1038/leu.2011.273

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