Table of Content

Open Access iconOpen Access

ARTICLE

Downregulation of CREB Promotes Cell Proliferation by Mediating G1/S Phase Transition in Hodgkin Lymphoma

Fangjin Lu*†, Ying Zheng, Paul Owusu Donkor*, Peng Zou§, Ping Mu

* Tianjin State Key Laboratory of Modern Chinese Medicine, School of Chinese Materia Medica, Tianjin University of Traditional Chinese Medicine, Tianjin, China
† Department of Biochemistry, Nagoya University Graduate School of Medicine, Nagoya, Japan
‡ Clinical Lab, The Second Hospital Affiliated to Shenyang Medical College, Shenyang, Liaoning, China
§ Department of Biochemistry and Molecular Biology, Shenyang Medical College, Shenyang, Liaoning, China

Oncology Research 2016, 24(3), 171-179. https://doi.org/10.3727/096504016X14634208142987

Abstract

The cyclic-AMP response element-binding protein (CREB), a well-known nuclear transcription factor, has been shown to play an essential role in many cellular processes, including differentiation, cell survival, and cell proliferation, by regulating the expression of downstream genes. Recently, increased expression of CREB was frequently found in various tumors, indicating that CREB is implicated in the process of tumorigenesis. However, the effects of CREB on Hodgkin lymphoma (HL) remain unknown. To clarify the role of CREB in HL, we performed knockdown experiments in HL. We found that downregulation of CREB by short hairpin RNA (shRNA) resulted in enhancement of cell proliferation and promotion of G1/S phase transition, and these effects can be rescued by expression of shRNA-resistant CREB. Meanwhile, the expression level of cell cycle-related proteins, such as cyclin D1, cyclin E1, cyclin-dependent kinase 2 (CDK2), and CDK4, was elevated in response to depletion of CREB. Furthermore, we performed chromatin immunoprecipitation (ChIP) assay and confirmed that CREB directly bound to the promoter regions of these genes, which consequently contributed to the regulation of cell cycle. Consistent with our results, a clinical database showed that high expression of CREB correlates with favorable prognosis in B-cell lymphoma patients, which is totally different from the function of CREB in other cancers such as colorectal cancer, acute myeloid leukemia, and some endocrine cancers. Taken together, all of these features of CREB in HL strongly support its role as a tumor suppressor gene that can decelerate cell proliferation by inhibiting the expression of several cell cycle-related genes. Our results provide new evidence for prognosis prediction of HL and a promising therapeutic strategy for HL patients.

Keywords


Cite This Article

APA Style
Lu, F., Zheng, Y., Donkor, P.O., Zou, P., Mu, P. (2016). Downregulation of CREB promotes cell proliferation by mediating g1/s phase transition in hodgkin lymphoma. Oncology Research, 24(3), 171-179. https://doi.org/10.3727/096504016X14634208142987
Vancouver Style
Lu F, Zheng Y, Donkor PO, Zou P, Mu P. Downregulation of CREB promotes cell proliferation by mediating g1/s phase transition in hodgkin lymphoma. Oncol Res. 2016;24(3):171-179 https://doi.org/10.3727/096504016X14634208142987
IEEE Style
F. Lu, Y. Zheng, P.O. Donkor, P. Zou, and P. Mu "Downregulation of CREB Promotes Cell Proliferation by Mediating G1/S Phase Transition in Hodgkin Lymphoma," Oncol. Res., vol. 24, no. 3, pp. 171-179. 2016. https://doi.org/10.3727/096504016X14634208142987



cc This work is licensed under a Creative Commons Attribution 4.0 International License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
  • 34

    View

  • 21

    Download

  • 0

    Like

Share Link