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Transcriptional activation of CBFβ by CDK11p110 is necessary to promote osteosarcoma cell proliferation

Authors
  • Feng, Yong1, 2
  • Liao, Yunfei1, 2
  • Zhang, Jianming2
  • Shen, Jacson2
  • Shao, Zengwu1
  • Hornicek, Francis2
  • Duan, Zhenfeng2
  • 1 Huazhong University of Science and Technology, Department of Orthopaedic Surgery, Wuhan Union Hospital, Tongji Medical College, 1277 Jie Fang Avenue, Wuhan, 430022, China , Wuhan (China)
  • 2 David Geffen School of Medicine at UCLA, Sarcoma Biology Laboratory, Department of Orthopaedic Surgery, Department of Orthopaedic Surgery, 615 Charles E. Young Dr. S, Los Angeles, CA, 90095, USA , Los Angeles (United States)
Type
Published Article
Journal
Cell Communication and Signaling
Publisher
BioMed Central
Publication Date
Oct 14, 2019
Volume
17
Issue
1
Identifiers
DOI: 10.1186/s12964-019-0440-5
Source
Springer Nature
Keywords
License
Green

Abstract

BackgroundAberrant expression of cyclin-dependent protein kinases (CDK) is a hallmark of cancer. CDK11 plays a crucial role in cancer cell growth and proliferation. However, the molecular mechanisms of CDK11 and CDK11 transcriptionally regulated genes are largely unknown.MethodsIn this study, we performed a global transcriptional analysis using gene array technology to investigate the transcriptional role of CDK11 in osteosarcoma. The promoter luciferase assay, chromatin immunoprecipitation assay, and Gel Shift assay were used to identify direct transcriptional targets of CDK11. Clinical relevance and function of core-binding factor subunit beta (CBFβ) were further accessed in osteosarcoma.ResultsWe identified a transcriptional role of protein-DNA interaction for CDK11p110, but not CDK11p58, in the regulation of CBFβ expression in osteosarcoma cells. The CBFβ promoter luciferase assay, chromatin immunoprecipitation assay, and Gel Shift assay confirmed that CBFβ is a direct transcriptional target of CDK11. High expression of CBFβ is associated with poor outcome in osteosarcoma patients. Expression of CBFβ contributes to the proliferation and metastatic behavior of osteosarcoma cells.ConclusionsThese data establish CBFβ as a mediator of CDK11p110 dependent oncogenesis and suggest that targeting the CDK11- CBFβ pathway may be a promising therapeutic strategy for osteosarcoma treatment.Graphical Abstract

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