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MicroRNA-192 regulates cell proliferation and cell cycle transition in acute myeloid leukemia via interaction with CCNT2

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Abstract

MicroRNAs (miRNAs) are a class of small non-coding RNAs approximately 18–22 nucleotides in length, which play an important role in malignant transformation. The roles of miR-192 as an oncogene or tumor suppressor in solid tumors have been previously reported. However, little is known about the role of miR-192 in human acute myeloid leukemia. The results of the present study indicate that miR-192 is significantly downregulated in specimens from acute myeloid leukemia patients. Functional assays demonstrated that overexpression of miR-192 in NB4 and HL-60 cells significantly inhibited cell proliferation compared with that in control cells, and induced G0/G1 cell cycle arrest, cell differentiation, and apoptosis in vitro. Dual-luciferase reporter gene assays showed that miR-192 significantly suppressed the activity of a reporter gene containing the wild type 3′-UTR of CCNT2, but it did not suppress the activity of a reporter gene containing mutated 3′-UTR of CCNT2. QRT-PCR and Western blot assays showed that miR-192 significantly downregulated the expression of CCNT2 in human leukemia cells. Exogenous expression of CCNT2 attenuated the cell cycle arrest induced by miR-192 in NB4 and HL-60 cells. Collectively, miR-192 inhibits cell proliferation and induces G0/G1 cell cycle arrest in AML by regulating the expression of CCNT2.

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Acknowledgements

The authors thank the local doctors and the patients who participated in our study. The project was supported by the Hubei Provincial Natural Science Foundation of China (No. 2011CDD193).

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Authors and Affiliations

  1. Department of Emergency Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China

    Shun Ke, Jun Lu, Yi-kuan Feng & Ming-hao Fang

  2. Department of General Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China

    Rui-chao Li

  3. Department of Hematology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China

    Fan-kai Meng

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  1. Shun Ke
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  2. Rui-chao Li
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Correspondence to Ming-hao Fang.

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Ke, S., Li, Rc., Lu, J. et al. MicroRNA-192 regulates cell proliferation and cell cycle transition in acute myeloid leukemia via interaction with CCNT2. Int J Hematol 106, 258–265 (2017). https://doi.org/10.1007/s12185-017-2232-2

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  • DOI: https://doi.org/10.1007/s12185-017-2232-2

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