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Article

Cullin-5, a ubiquitin ligase scaffold protein, is significantly underexpressed in endometrial adenocarcinomas and is a target of miR-182

  • Authors:
    • Eric J. Devor
    • Brandon M. Schickling
    • Henry D. Reyes
    • Akshaya Warrier
    • Brittany Lindsay
    • Michael J. Goodheart
    • Donna A. Santillan
    • Kimberly K. Leslie
  • View Affiliations / Copyright

    Affiliations: Department of Obstetrics and Gynecology, University of Iowa Carver College of Medicine, Iowa City, IA 52242, USA, Department of Internal Medicine, University of Iowa Carver College of Medicine, Iowa City, IA 52242, USA
  • Pages: 2461-2465
    |
    Published online on: February 1, 2016
       https://doi.org/10.3892/or.2016.4605
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Abstract

Altered expression of cullin-5 (CUL5), a member of the cullin-RING E3 ubiquitin ligase family, has been implicated in a number of types of cancers including breast, cervical and hepatocellular cancers. In the present study, we found that CUL5 expression was significantly decreased in both endometrioid and serous endometrial adenocarcinomas with the more aggressive serous type displaying a higher reduction (-4.3-fold) than the less aggressive endometrioid type (-2.9-fold). Overexpression of CUL5 mRNA and protein in Ishikawa H endometrial cancer cells resulted in decreased cell proliferation and in a reduction in CUL5-RING E3 ligase downstream clients JAK2 and FAS-L. Finally, we demonstrated for the first time that CUL5 is a direct target of miR-182 that we previously showed to be significantly overexpressed in endometrial adenocarcinomas and we provided evidence that increased miR-182 expression is, at least in part, a result of demethylation of its upstream promoter. These data suggest a cascade in which miR-182 expression is epigenetically increased leading to decreased CUL5 expression and increased cellular proliferation. The final step in the cascade may be operating through a decrease in ubiquitination of pro-growth CUL5 ubiquitin ligase clients. This cascade offers a series of potential interventional steps involving epigenetic modification, miRNA and/or gene targeting and ubiquitination.
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Copy and paste a formatted citation
Spandidos Publications style
Devor EJ, Schickling BM, Reyes HD, Warrier A, Lindsay B, Goodheart MJ, Santillan DA and Leslie KK: Cullin-5, a ubiquitin ligase scaffold protein, is significantly underexpressed in endometrial adenocarcinomas and is a target of miR-182. Oncol Rep 35: 2461-2465, 2016.
APA
Devor, E.J., Schickling, B.M., Reyes, H.D., Warrier, A., Lindsay, B., Goodheart, M.J. ... Leslie, K.K. (2016). Cullin-5, a ubiquitin ligase scaffold protein, is significantly underexpressed in endometrial adenocarcinomas and is a target of miR-182. Oncology Reports, 35, 2461-2465. https://doi.org/10.3892/or.2016.4605
MLA
Devor, E. J., Schickling, B. M., Reyes, H. D., Warrier, A., Lindsay, B., Goodheart, M. J., Santillan, D. A., Leslie, K. K."Cullin-5, a ubiquitin ligase scaffold protein, is significantly underexpressed in endometrial adenocarcinomas and is a target of miR-182". Oncology Reports 35.4 (2016): 2461-2465.
Chicago
Devor, E. J., Schickling, B. M., Reyes, H. D., Warrier, A., Lindsay, B., Goodheart, M. J., Santillan, D. A., Leslie, K. K."Cullin-5, a ubiquitin ligase scaffold protein, is significantly underexpressed in endometrial adenocarcinomas and is a target of miR-182". Oncology Reports 35, no. 4 (2016): 2461-2465. https://doi.org/10.3892/or.2016.4605
Copy and paste a formatted citation
x
Spandidos Publications style
Devor EJ, Schickling BM, Reyes HD, Warrier A, Lindsay B, Goodheart MJ, Santillan DA and Leslie KK: Cullin-5, a ubiquitin ligase scaffold protein, is significantly underexpressed in endometrial adenocarcinomas and is a target of miR-182. Oncol Rep 35: 2461-2465, 2016.
APA
Devor, E.J., Schickling, B.M., Reyes, H.D., Warrier, A., Lindsay, B., Goodheart, M.J. ... Leslie, K.K. (2016). Cullin-5, a ubiquitin ligase scaffold protein, is significantly underexpressed in endometrial adenocarcinomas and is a target of miR-182. Oncology Reports, 35, 2461-2465. https://doi.org/10.3892/or.2016.4605
MLA
Devor, E. J., Schickling, B. M., Reyes, H. D., Warrier, A., Lindsay, B., Goodheart, M. J., Santillan, D. A., Leslie, K. K."Cullin-5, a ubiquitin ligase scaffold protein, is significantly underexpressed in endometrial adenocarcinomas and is a target of miR-182". Oncology Reports 35.4 (2016): 2461-2465.
Chicago
Devor, E. J., Schickling, B. M., Reyes, H. D., Warrier, A., Lindsay, B., Goodheart, M. J., Santillan, D. A., Leslie, K. K."Cullin-5, a ubiquitin ligase scaffold protein, is significantly underexpressed in endometrial adenocarcinomas and is a target of miR-182". Oncology Reports 35, no. 4 (2016): 2461-2465. https://doi.org/10.3892/or.2016.4605
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