Journal article
R1 Regulates Prostate Tumor Growth and Progression By Transcriptional Suppression of the E3 Ligase HUWE1 to Stabilize c-Myc
Molecular cancer research, Vol.16(12), pp.1940-1951
12/2018
PMID: 30042175
Abstract
Prostate cancer is a prevalent public health problem, especially because noncutaneous advanced malignant forms significantly affect the lifespan and quality of life of men worldwide. New therapeutic targets and approaches are urgently needed. The current study reports elevated expression of R1 (CDCA7L/RAM2/JPO2), a c-Myc-interacting protein and transcription factor, in human prostate cancer tissue specimens. In a clinical cohort, high R1 expression is associated with disease recurrence and decreased patient survival. Overexpression and knockdown of R1 in human prostate cancer cells indicate that R1 induces cell proliferation and colony formation. Moreover, silencing R1 dramatically reduces the growth of prostate tumor xenografts in mice. Mechanistically, R1 increases c-Myc protein stability by inhibiting ubiquitination and proteolysis through transcriptional suppression of
, a c-Myc-targeting E3 ligase, via direct interaction with a binding element in the promoter. Moreover, transcriptional repression is supported by a negative coexpression correlation between
and
in a prostate cancer clinical dataset. Collectively, these findings, for the first time, characterize the contribution of R1 to prostate cancer pathogenesis. IMPLICATIONS: These findings provide evidence that R1 is a novel regulator of prostate tumor growth by stabilizing c-Myc protein, meriting further investigation of its therapeutic and prognostic potential.
Metrics
27 File views/ downloads
6 Record Views
Details
- Title
- R1 Regulates Prostate Tumor Growth and Progression By Transcriptional Suppression of the E3 Ligase HUWE1 to Stabilize c-Myc
- Creators
- Tzu-Ping Lin - National Yang Ming UniversityJingjing Li - Washington State University SpokaneQinlong Li - Xijing HospitalXiangyan Li - Cedars-Sinai Medical CenterChunyan Liu - Cedars-Sinai Medical CenterNi Zeng - University of Southern CaliforniaJen-Ming Huang - Cedars-Sinai Medical CenterGina Chia-Yi Chu - Cedars-Sinai Medical CenterChi-Hung Lin - National Yang Ming UniversityHaiyen E Zhau - Cedars-Sinai Medical CenterLeland W K Chung - Cedars-Sinai Medical CenterBoyang Jason Wu - Washington State University, Pharmaceutical Sciences, Department of
- Publication Details
- Molecular cancer research, Vol.16(12), pp.1940-1951
- Academic Unit
- Pharmacy and Pharmaceutical Sciences, College of
- Identifiers
- 99900620489801842
- Language
- English
- Resource Type
- Journal article