Jun Lu1,2,3, Zhan Chen4, Hu Zhao5,4,6, Huiyue Dong5,4,6, Ling Zhu5,4,6, Yi Zhang4, Jie Wang4, Hehuan Zhu4, Qiang Cui4, Chuang Qi5, Shuiliang Wang5,4,6, Shushang Chen6, Jichun Shao7. 1. Fujian Provincial Key Laboratory of Transplant Biology, Fuzhou General Clinical College, Fujian Medical University, Fuzhou, 350025, China. junlu.heather@xmu.edu.cn. 2. Fujian Provincial Key Laboratory of Transplant Biology, Dongfang Hospital (900 Hospital of the Joint Logistics Team), Xiamen University, Fuzhou, 350025, China. junlu.heather@xmu.edu.cn. 3. Department of Urology, 900 Hospital of the Joint Logistics Team, Fuzhou, 350025, Fujian, China. junlu.heather@xmu.edu.cn. 4. Fujian Provincial Key Laboratory of Transplant Biology, Dongfang Hospital (900 Hospital of the Joint Logistics Team), Xiamen University, Fuzhou, 350025, China. 5. Fujian Provincial Key Laboratory of Transplant Biology, Fuzhou General Clinical College, Fujian Medical University, Fuzhou, 350025, China. 6. Department of Urology, 900 Hospital of the Joint Logistics Team, Fuzhou, 350025, Fujian, China. 7. Department of Urology, Second Affiliated Hospital of Chengdu Medical College (China National Nuclear Corporation 416 Hospital), Chengdu, 610051, China. shaoji93@163.com.
Abstract
BACKGROUND: Clear cell renal cell carcinoma (ccRCC) is a malignancy characterized by metabolic reprogramming. ABAT and ALDH6A1 are metabolic enzymes. In this study, we aim to investigate the associations of ABAT and ALDH6A1 with the malignancy of ccRCC cells. METHODS: The gene expression levels of ABAT and ALDH6A1 in ccRCC were analyzed from gene expression microarray datasets and RNA sequencing data. Clinical information was analyzed from The Cancer Genome Atlas (TCGA) data. The distributions of ABAT and ALDH6A1 in ccRCC clinical tissues were screened by reverse transcription-quantitative polymerase chain reaction (RT-QPCR) and immunohistochemical assays. The effect of overexpression of ABAT or ALDH6A1 was measured by detecting the cell viability, migration ability, and the ratio of lactate and nicotinamide adenine dinucleotide phosphate (NADPH). Chromatin immunoprecipitation (ChIP) and luciferase reporter assays were carried out to investigate the transcript regulation of HNF4A in ABAT and ALDH6A1. RESULTS: Remarkable downregulated ABAT and ALDH6A1 expression levels were observed in ccRCC patients and low expression of ABAT and ALDH6A1 was correlated with poor survival. Overexpression of ABAT or ALDH6A1 significantly attenuated cell proliferation and migration, and impaired lactate production. In ABAT increased ccRCC cells, the ratio of NADPH/NADP+ was reduced. Finally, we demonstrated that ABAT and ALDH6A1 were directly regulated by a tumor suppressor, HNF4A. CONCLUSIONS: These observations identified HNF4A-regulated low-expressed ABAT and ALDH6A1 as promising diagnostic and prognostic biomarkers for ccRCC.
BACKGROUND: Clear cell renal cell carcinoma (ccRCC) is a malignancy characterized by metabolic reprogramming. ABAT and ALDH6A1 are metabolic enzymes. In this study, we aim to investigate the associations of ABAT and ALDH6A1 with the malignancy of ccRCC cells. METHODS: The gene expression levels of ABAT and ALDH6A1 in ccRCC were analyzed from gene expression microarray datasets and RNA sequencing data. Clinical information was analyzed from The Cancer Genome Atlas (TCGA) data. The distributions of ABAT and ALDH6A1 in ccRCC clinical tissues were screened by reverse transcription-quantitative polymerase chain reaction (RT-QPCR) and immunohistochemical assays. The effect of overexpression of ABAT or ALDH6A1 was measured by detecting the cell viability, migration ability, and the ratio of lactate and nicotinamide adenine dinucleotide phosphate (NADPH). Chromatin immunoprecipitation (ChIP) and luciferase reporter assays were carried out to investigate the transcript regulation of HNF4A in ABAT and ALDH6A1. RESULTS: Remarkable downregulated ABAT and ALDH6A1 expression levels were observed in ccRCC patients and low expression of ABAT and ALDH6A1 was correlated with poor survival. Overexpression of ABAT or ALDH6A1 significantly attenuated cell proliferation and migration, and impaired lactate production. In ABAT increased ccRCC cells, the ratio of NADPH/NADP+ was reduced. Finally, we demonstrated that ABAT and ALDH6A1 were directly regulated by a tumor suppressor, HNF4A. CONCLUSIONS: These observations identified HNF4A-regulated low-expressed ABAT and ALDH6A1 as promising diagnostic and prognostic biomarkers for ccRCC.
Authors: Jon Jones; Hasan Otu; Dimitrios Spentzos; Shakirahmed Kolia; Mehmet Inan; Wolf D Beecken; Christian Fellbaum; Xuesong Gu; Marie Joseph; Allan J Pantuck; Dietger Jonas; Towia A Libermann Journal: Clin Cancer Res Date: 2005-08-15 Impact factor: 12.531
Authors: Karthikeyani Chellappa; Poonamjot Deol; Jane R Evans; Linh M Vuong; Gang Chen; Nadege Briançon; Eugene Bolotin; Christian Lytle; Meera G Nair; Frances M Sladek Journal: Elife Date: 2016-05-11 Impact factor: 8.140
Authors: Jörn Oliver Sass; Melanie Walter; Julian P H Shield; Andrea M Atherton; Uttam Garg; David Scott; C Geoffrey Woods; Laurie D Smith Journal: J Inherit Metab Dis Date: 2011-08-24 Impact factor: 4.982
Authors: Michelle L Gumz; Hongzhi Zou; Pamela A Kreinest; April C Childs; Leandra S Belmonte; Shauna N LeGrand; Kevin J Wu; Bruce A Luxon; Mala Sinha; Alexander S Parker; L-Z Sun; David A Ahlquist; Christopher G Wood; John A Copland Journal: Clin Cancer Res Date: 2007-08-15 Impact factor: 12.531