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Article

UHRF1 regulates the transcriptional repressor HBP1 through MIF in T acute lymphoblastic leukemia

  • Authors:
    • Jie Yao
    • Yaosheng Luo
    • Chong Zeng
    • Haiyan He
    • Xiaoli Zhang
  • View Affiliations / Copyright

    Affiliations: Department of Laboratory Medicine and Medical Research Center, Shunde Hospital, Southern Medical University (The First People's Hospital of Shunde Foshan), Foshan, Guangdong 528300, P.R. China, Department of Laboratory Medicine, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing 400038, P.R. China
  • Article Number: 131
    |
    Published online on: May 18, 2021
       https://doi.org/10.3892/or.2021.8082
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Abstract

Macrophage migration inhibitory factor (MIF) has been confirmed as an oncogene in solid tumor development, and its overexpression causes cell proliferation in T acute lymphoblastic leukemia (T‑ALL); however, the underlying mechanisms remain unclear. The overexpression of MIF promotes cellular transformation and proliferation, in part, through interaction with UHRF1. Nevertheless, overexpression of UHRF1 cannot upregulate MIF expression in T‑ALL. New insights into MIF regulation in T‑ALL are imperative to offer the opportunity for therapeutic intervention. In the present study, using RT‑qPCR, western blot analysis, confocal microscopy and RNA sequence, we report the identification and validation of UHRF1 as a negative regulator of MIF, which functions to downregulate MIF expression by binding to the CATT repeat sequence of the MIF promoter. By contrast, HMG‑box protein 1 (HBP1) functions as a positive regulator of MIF. Moreover, we demonstrated that HBP1 suppressive signaling is reduced by UHRF1 through promotion of the interaction between MIF and HBP1. MIF deficiency caused by UHRF1 knockdown resulted in enhanced apoptosis in T‑ALL as compared with that caused by decreased MIF or increased HBP1 expression alone. These results identify UHRF1 as a key regulator of MIF transcription in T‑ALL, although these transcription factors possess opposite regulatory functions. Thus, this mechanism may provide insight into how to effectively prevent MIF‑dependent oncogenic activity. Finally, T‑ALL mice possessing high HBP1 or low UHRF1 expression levels are associated with longer survival as compared with control mice, with UHRF1‑knockdown mice living the longest. Taken together, these findings indicate that MIF and its regulators are potential treatment targets and biomarkers for the prediction of prognosis in T‑ALL.
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Copy and paste a formatted citation
Spandidos Publications style
Yao J, Luo Y, Zeng C, He H and Zhang X: UHRF1 regulates the transcriptional repressor HBP1 through MIF in T acute lymphoblastic leukemia. Oncol Rep 46: 131, 2021.
APA
Yao, J., Luo, Y., Zeng, C., He, H., & Zhang, X. (2021). UHRF1 regulates the transcriptional repressor HBP1 through MIF in T acute lymphoblastic leukemia. Oncology Reports, 46, 131. https://doi.org/10.3892/or.2021.8082
MLA
Yao, J., Luo, Y., Zeng, C., He, H., Zhang, X."UHRF1 regulates the transcriptional repressor HBP1 through MIF in T acute lymphoblastic leukemia". Oncology Reports 46.1 (2021): 131.
Chicago
Yao, J., Luo, Y., Zeng, C., He, H., Zhang, X."UHRF1 regulates the transcriptional repressor HBP1 through MIF in T acute lymphoblastic leukemia". Oncology Reports 46, no. 1 (2021): 131. https://doi.org/10.3892/or.2021.8082
Copy and paste a formatted citation
x
Spandidos Publications style
Yao J, Luo Y, Zeng C, He H and Zhang X: UHRF1 regulates the transcriptional repressor HBP1 through MIF in T acute lymphoblastic leukemia. Oncol Rep 46: 131, 2021.
APA
Yao, J., Luo, Y., Zeng, C., He, H., & Zhang, X. (2021). UHRF1 regulates the transcriptional repressor HBP1 through MIF in T acute lymphoblastic leukemia. Oncology Reports, 46, 131. https://doi.org/10.3892/or.2021.8082
MLA
Yao, J., Luo, Y., Zeng, C., He, H., Zhang, X."UHRF1 regulates the transcriptional repressor HBP1 through MIF in T acute lymphoblastic leukemia". Oncology Reports 46.1 (2021): 131.
Chicago
Yao, J., Luo, Y., Zeng, C., He, H., Zhang, X."UHRF1 regulates the transcriptional repressor HBP1 through MIF in T acute lymphoblastic leukemia". Oncology Reports 46, no. 1 (2021): 131. https://doi.org/10.3892/or.2021.8082
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