Skip to main content

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

Publication ,  Journal Article
Devor, EJ; Schickling, BM; Reyes, HD; Warrier, A; Lindsay, B; Goodheart, MJ; Santillan, DA; Leslie, KK
Published in: Oncol Rep
April 2016

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.

Duke Scholars

Altmetric Attention Stats
Dimensions Citation Stats

Published In

Oncol Rep

DOI

EISSN

1791-2431

Publication Date

April 2016

Volume

35

Issue

4

Start / End Page

2461 / 2465

Location

Greece

Related Subject Headings

  • Signal Transduction
  • Promoter Regions, Genetic
  • MicroRNAs
  • Humans
  • Gene Expression Regulation, Neoplastic
  • Female
  • Endometrial Neoplasms
  • Down-Regulation
  • DNA Methylation
  • Cullin Proteins
 

Citation

APA
Chicago
ICMJE
MLA
NLM
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. Oncol Rep, 35(4), 2461–2465. https://doi.org/10.3892/or.2016.4605
Devor, Eric J., Brandon M. Schickling, Henry D. Reyes, Akshaya Warrier, Brittany Lindsay, Michael J. Goodheart, Donna A. Santillan, and Kimberly K. Leslie. “Cullin-5, a ubiquitin ligase scaffold protein, is significantly underexpressed in endometrial adenocarcinomas and is a target of miR-182.Oncol Rep 35, no. 4 (April 2016): 2461–65. https://doi.org/10.3892/or.2016.4605.
Devor EJ, Schickling BM, Reyes HD, Warrier A, Lindsay B, Goodheart MJ, et al. Cullin-5, a ubiquitin ligase scaffold protein, is significantly underexpressed in endometrial adenocarcinomas and is a target of miR-182. Oncol Rep. 2016 Apr;35(4):2461–5.
Devor, Eric J., et al. “Cullin-5, a ubiquitin ligase scaffold protein, is significantly underexpressed in endometrial adenocarcinomas and is a target of miR-182.Oncol Rep, vol. 35, no. 4, Apr. 2016, pp. 2461–65. Pubmed, doi:10.3892/or.2016.4605.
Devor EJ, Schickling BM, Reyes HD, Warrier A, Lindsay B, Goodheart MJ, Santillan DA, Leslie KK. Cullin-5, a ubiquitin ligase scaffold protein, is significantly underexpressed in endometrial adenocarcinomas and is a target of miR-182. Oncol Rep. 2016 Apr;35(4):2461–2465.

Published In

Oncol Rep

DOI

EISSN

1791-2431

Publication Date

April 2016

Volume

35

Issue

4

Start / End Page

2461 / 2465

Location

Greece

Related Subject Headings

  • Signal Transduction
  • Promoter Regions, Genetic
  • MicroRNAs
  • Humans
  • Gene Expression Regulation, Neoplastic
  • Female
  • Endometrial Neoplasms
  • Down-Regulation
  • DNA Methylation
  • Cullin Proteins