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© 2019. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.

Abstract

DAPK, a transcriptional target of the p53 protein, has long been characterized as a tumor suppressor that acts as a negative regulator in multiple cellular processes. However, increasing studies have suggested that the role of DAPK may vary depending on cell type and cellular context. Thus far, the expression and function of DAPK in clear cell renal cell carcinoma (ccRCC) remain ambiguous. Since ccRCC behaves in an atypical way with respect to p53, whether the p53‐DAPK axis functions normally in ccRCC is also an intriguing question. Here, tissue specimens from 61 ccRCC patients were examined for DAPK expression. Functional studies regarding apoptosis, growth, and migration were used to determine the role of DAPK in renal cancer cells. The validity of the p53‐DAPK axis in ccRCC was also determined. Our study identified DAPK as a negative regulator of ccRCC, and its expression was reduced in certain subgroups. However, the p53‐DAPK axis was disrupted due to upregulation of miR‐34a‐5p under stressed conditions. miR‐34a‐5p was identified as a novel repressor of DAPK acting downstream of p53. Inhibition of miR‐34a‐5p can correct the p53‐DAPK axis disruption by upregulating DAPK protein and may have potential to be used as a therapeutic target to improve outcomes for ccRCC patients.

Details

Title
Inhibition of miR‐34a‐5p can rescue disruption of the p53‐DAPK axis to suppress progression of clear cell renal cell carcinoma
Author
Zhi‐Fei Jing 1 ; Jian‐Bin Bi 1 ; Li, Zeliang 1 ; Liu, Xiankui 1 ; Li, Jun 1 ; Zhu, Yuyan 1 ; Xiao‐Tong Zhang 1 ; Zhang, Zhe 1 ; Li, Zhenhua 1 ; Chui‐Ze Kong 1   VIAFID ORCID Logo 

 Department of Urology, First Hospital of China Medical University, Shenyang, Liaoning, China; Institute of Urology, China Medical University, Shenyang, China 
Pages
2079-2097
Section
Research Articles
Publication year
2019
Publication date
Oct 2019
Publisher
John Wiley & Sons, Inc.
ISSN
15747891
e-ISSN
18780261
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
2297847605
Copyright
© 2019. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.