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Zhou X, Gan L, Liu J, et al. Pirarubicin reduces USP22 expression by inhibiting CREB-1 phosphorylation in HeLa cells. Exp Ther Med. 2019;17(5):4230-4236doi: 10.3892/etm.2019.7447.
Zhou, X., Gan, L., Liu, J., Xie, X., Wang, T., & Xiong, J. (2019). Pirarubicin reduces USP22 expression by inhibiting CREB-1 phosphorylation in HeLa cells. Experimental and therapeutic medicine, 17(5), 4230-4236. https://doi.org/10.3892/etm.2019.7447
Zhou, Xiaoou, et al. "Pirarubicin reduces USP22 expression by inhibiting CREB-1 phosphorylation in HeLa cells." Experimental and therapeutic medicine vol. 17,5 (2019): 4230-4236. doi: https://doi.org/10.3892/etm.2019.7447
Zhou X, Gan L, Liu J, Xie X, Wang T, Xiong J. Pirarubicin reduces USP22 expression by inhibiting CREB-1 phosphorylation in HeLa cells. Exp Ther Med. 2019 May;17(5):4230-4236. doi: 10.3892/etm.2019.7447. Epub 2019 Mar 27. PMID: 31007754; PMCID: PMC6468931.
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Exp Ther Med. 2019 May;17(5):4230-4236. doi: 10.3892/etm.2019.7447. Epub 2019 Mar 27.

Pirarubicin reduces USP22 expression by inhibiting CREB-1 phosphorylation in HeLa cells.

Experimental and therapeutic medicine

Xiaoou Zhou, Lijun Gan, Jianyun Liu, Xin Xie, Tao Wang, Jianjun Xiong

Affiliations

  1. Department of Pharmacology, College of Basic Medical Science, Jiujiang University, Jiujiang, Jiangxi 332000, P.R. China.
  2. Department of Clinical Nursing, College of Nursing, Jiujiang University, Jiujiang, Jiangxi 332000, P.R. China.
  3. Key Laboratory of Jiangxi Province for The Systems Biomedicine, Jiujiang, Jiangxi 332000, P.R. China.

PMID: 31007754 PMCID: PMC6468931 DOI: 10.3892/etm.2019.7447

Abstract

The expression of ubiquitin specific peptidase 22 (USP22) is upregulated in several types of cancer, and has been implicated in tumorigenesis. Pirarubicin (THP), an anthracycline antineoplastic drug, can induce apoptosis of several types of cancer cells. However, the molecular mechanisms underlying the action of THP remain to be elucidated. In the current study, treatment with THP induced HeLa cell apoptosis and decreased USP22 expression in a dose- and time-dependent manner. THP reduced the USP22 promoter-regulated luciferase activity, regardless of the mutation of transcriptional activator MYB or E3 ubiquitin-protein ligase SP1 binding sequences; however, this effect was abrogated by the mutation of cyclic AMP-responsive element-binding protein (CREB) binding sequence in HeLa cells. Furthermore, the inhibition on the USP22 promoter activity by THP was not affected by overexpression of CREB-1 in HeLa cells. Additionally, treatment with THP significantly decreased the phosphorylation of CREB-1 at ser133 in HeLa cells. Quantitative chromatin immunoprecipitation assay revealed that THP significantly inhibited the binding of CREB-1 to the USP22 promoter in HeLa cells. The present study demonstrated that THP decreased USP22 expression and promoted HeLa cell apoptosis partially by inhibiting the phosphorylation of CREB-1. The current results may provide novel insights into the molecular mechanisms underlying the pharmacological effect of THP on cancer cell apoptosis.

Keywords: HeLa; cyclic AMP-responsive element-binding protein-1; phosphorylation; pirarubicin; ubiquitin specific peptidase 22

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