Denise R. Minton
Role of NADH Dehydrogenase (Ubiquinone) 1 Alpha Subcomplex 4-Like 2 in Clear Cell Renal Cell Carcinoma
Minton, Denise R.; Fu, Leiping; Mongan, Nigel P.; Shevchuk, Maria M.; Nanus, David M.; Gudas, Lorraine J.
NIGEL MONGAN email@example.com
Professor of Oncology
Maria M. Shevchuk
David M. Nanus
Lorraine J. Gudas
We delineated the functions of the HIF1α target NADH Dehydrogenase (Ubiquinone) 1 alpha subcomplex 4-like 2 (NDUFA4L2) in ccRCC and characterized NDUFA4L2 as a novel molecular target for ccRCC treatment.
We evaluated normal kidney and ccRCC patient microarray and RNAseq data from Oncomine and The Cancer Genome Atlas (TCGA) for NDUFA4L2 mRNA levels and the clinical implications of high NDUFA4L2 expression. Additionally, we examined normal kidney and ccRCC patient tissue samples, human ccRCC cell lines, and murine models of ccRCC for NDUFA4L2 mRNA and protein expression. Utilizing shRNA, we performed NDUFA4L2 knockdown experiments and analyzed the proliferation, clonogenicity, metabolite levels, cell structure, and autophagy in ccRCC cell lines in culture.
We found that NDUFA4L2 mRNA and protein are highly expressed in ccRCC samples but undetectable in normal kidney tissue samples, and that NDUFA4L2 mRNA expression correlates with tumor stage and lower overall survival. Additionally, we demonstrated that NDUFA4L2 is a HIF1α target in ccRCC and that NDUFA4L2 knockdown has a profound anti-proliferative effect, alters metabolic pathways, and causes major stress in cultured RCC cells.
Collectively, our data show that NDUFA4L2 is a novel molecular target for ccRCC treatment.
|Journal Article Type||Article|
|Publication Date||Jun 1, 2016|
|Journal||Clinical Cancer Research|
|Publisher||American Association for Cancer Research|
|Peer Reviewed||Peer Reviewed|
|APA6 Citation||Minton, D. R., Fu, L., Mongan, N. P., Shevchuk, M. M., Nanus, D. M., & Gudas, L. J. (2016). Role of NADH Dehydrogenase (Ubiquinone) 1 Alpha Subcomplex 4-Like 2 in Clear Cell Renal Cell Carcinoma. Clinical Cancer Research, 22(11), 2791-2801. https://doi.org/10.1158/1078-0432.ccr-15-1511|
|Copyright Statement||Copyright information regarding this work can be found at the following address: http://eprints.nottingh.../end_user_agreement.pdf|
Clin Cancer Res-2016-Minton-1078-0432.CCR-15-1511.pdf
Copyright information regarding this work can be found at the following address: http://eprints.nottingham.ac.uk/end_user_agreement.pdf
You might also like
Molecular Characterisation of Canine Osteosarcoma in High Risk Breeds
Elevated MMP9 expression in breast cancer is a predictor of shorter patient survival
A novel prognostic two-gene signature for triple negative breast cancer