Role of NADH Dehydrogenase (Ubiquinone) 1 alpha subcomplex 4-like 2 in clear cell renal cell carcinoma
PURPOSE 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. EXPERIMENTAL DESIGN We evaluated normal kidney and ccRCC patient microarray and...
| Main Authors: | , , , , , |
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| Format: | Article |
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American Association for Cancer Research
2016
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| Online Access: | https://eprints.nottingham.ac.uk/31392/ |
| _version_ | 1848794191739486208 |
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| author | Minton, Denise R. Fu, Leiping Mongan, Nigel P. Shevchuk, Maria M. Nanus, David M. Gudas, Lorraine J. |
| author_facet | Minton, Denise R. Fu, Leiping Mongan, Nigel P. Shevchuk, Maria M. Nanus, David M. Gudas, Lorraine J. |
| author_sort | Minton, Denise R. |
| building | Nottingham Research Data Repository |
| collection | Online Access |
| description | PURPOSE
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.
EXPERIMENTAL DESIGN
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.
RESULTS
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.
CONCLUSIONS
Collectively, our data show that NDUFA4L2 is a novel molecular target for ccRCC treatment. |
| first_indexed | 2025-11-14T19:12:16Z |
| format | Article |
| id | nottingham-31392 |
| institution | University of Nottingham Malaysia Campus |
| institution_category | Local University |
| last_indexed | 2025-11-14T19:12:16Z |
| publishDate | 2016 |
| publisher | American Association for Cancer Research |
| recordtype | eprints |
| repository_type | Digital Repository |
| spelling | nottingham-313922020-05-04T17:31:42Z https://eprints.nottingham.ac.uk/31392/ 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. PURPOSE 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. EXPERIMENTAL DESIGN 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. RESULTS 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. CONCLUSIONS Collectively, our data show that NDUFA4L2 is a novel molecular target for ccRCC treatment. American Association for Cancer Research 2016-01-18 Article PeerReviewed Minton, Denise R., Fu, Leiping, Mongan, Nigel P., Shevchuk, Maria M., Nanus, David M. and Gudas, Lorraine J. (2016) Role of NADH Dehydrogenase (Ubiquinone) 1 alpha subcomplex 4-like 2 in clear cell renal cell carcinoma. Clinical Cancer Research . ISSN 1557-3265 (In Press) http://clincancerres.aacrjournals.org/content/early/2016/01/16/1078-0432.CCR-15-1511 doi:10.1158/1078-0432.CCR-15-1511 doi:10.1158/1078-0432.CCR-15-1511 |
| spellingShingle | Minton, Denise R. Fu, Leiping Mongan, Nigel P. Shevchuk, Maria M. Nanus, David M. Gudas, Lorraine J. Role of NADH Dehydrogenase (Ubiquinone) 1 alpha subcomplex 4-like 2 in clear cell renal cell carcinoma |
| title | Role of NADH Dehydrogenase (Ubiquinone) 1 alpha subcomplex 4-like 2 in clear cell renal cell carcinoma |
| title_full | Role of NADH Dehydrogenase (Ubiquinone) 1 alpha subcomplex 4-like 2 in clear cell renal cell carcinoma |
| title_fullStr | Role of NADH Dehydrogenase (Ubiquinone) 1 alpha subcomplex 4-like 2 in clear cell renal cell carcinoma |
| title_full_unstemmed | Role of NADH Dehydrogenase (Ubiquinone) 1 alpha subcomplex 4-like 2 in clear cell renal cell carcinoma |
| title_short | Role of NADH Dehydrogenase (Ubiquinone) 1 alpha subcomplex 4-like 2 in clear cell renal cell carcinoma |
| title_sort | role of nadh dehydrogenase (ubiquinone) 1 alpha subcomplex 4-like 2 in clear cell renal cell carcinoma |
| url | https://eprints.nottingham.ac.uk/31392/ https://eprints.nottingham.ac.uk/31392/ https://eprints.nottingham.ac.uk/31392/ |