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A hnRNP K–AR-Related Signature Reflects Progression toward Castration-Resistant Prostate Cancer
Open AccessArticle

BRCA1 Interacting Protein COBRA1 Facilitates Adaptation to Castrate-Resistant Growth Conditions

1
Department of Urology, The University of Texas Health, San Antonio, TX 78229, USA
2
Pharmacology, the University of Texas Health, San Antonio, TX 78229, USA
3
Molecular Medicine, The University of Texas Health, San Antonio, TX 78229, USA
4
UT Health San Antonio Cancer Center, the University of Texas Health, San Antonio, TX 78229, USA
5
Pathology, the University of Texas Health, San Antonio, TX 78229, USA
6
Department of Urology, Massachusetts General Hospital Harvard Medical School, 55 Fruit Street, Yawkey Building, Suite 7E, Boston, MA 02215, USA
7
South Texas Veterans Health Care System, San Antonio, TX 78229, USA
*
Author to whom correspondence should be addressed.
Present address: Department of Pediatric Oncology, Dana-Farber Cancer Institute, Harvard Medical School, 450 Brookline Ave, Boston, MA 02142, USA.
Int. J. Mol. Sci. 2018, 19(7), 2104; https://doi.org/10.3390/ijms19072104
Received: 31 May 2018 / Revised: 22 June 2018 / Accepted: 12 July 2018 / Published: 20 July 2018
(This article belongs to the Special Issue Sex Hormone Receptor Signals in Human Malignancies)
COBRA1 (co-factor of BRCA1) is one of the four subunits of the negative elongation factor originally identified as a BRCA1-interacting protein. Here, we provide first-time evidence for the oncogenic role of COBRA1 in prostate pathogenesis. COBRA1 is aberrantly expressed in prostate tumors. It positively influences androgen receptor (AR) target gene expression and promoter activity. Depletion of COBRA1 leads to decreased cell viability, proliferation, and anchorage-independent growth in prostate cancer cell lines. Conversely, overexpression of COBRA1 significantly increases cell viability, proliferation, and anchorage-independent growth over the higher basal levels. Remarkably, AR-positive androgen dependent (LNCaP) cells overexpressing COBRA1 survive under androgen-deprivation conditions. Remarkably, treatment of prostate cancer cells with well-studied antitumorigenic agent, 2-methoxyestradiol (2-ME2), caused significant DNA methylation changes in 3255 genes including COBRA1. Furthermore, treatment of prostate cancer cells with 2-ME2 downregulates COBRA1 and inhibition of prostate tumors in TRAMP (transgenic adenocarcinomas of mouse prostate) animals with 2-ME2 was also associated with decreased COBRA1 levels. These observations implicate a novel role for COBRA1 in progression to CRPC and suggest that COBRA1 downregulation has therapeutic potential. View Full-Text
Keywords: COBRA1; NELFB; androgen receptor; CRPC COBRA1; NELFB; androgen receptor; CRPC
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Yun, H.; Bedolla, R.; Horning, A.; Li, R.; Chiang, H.-C.; Huang, T.-H.; Reddick, R.; Olumi, A.F.; Ghosh, R.; Kumar, A.P. BRCA1 Interacting Protein COBRA1 Facilitates Adaptation to Castrate-Resistant Growth Conditions. Int. J. Mol. Sci. 2018, 19, 2104.

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