Systematic expression analysis of the mitochondrial complex III subunits identifies UQCRC1 as biomarker in clear cell renal cell carcinoma
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Jörg Ellinger1, Arabella Gromes1, Mirjam Poss1, Maria Brüggemann1, Doris Schmidt1, Nadja Ellinger2, Yuri Tolkach3, Dimo Dietrich3,4, Glen Kristiansen3, Stefan C. Müller1
1University Hospital Bonn, Department of Urology, 53105 Bonn, Germany
2University Hospital Bonn, Department of Anesthesiology and Intensive Care, 53105 Bonn, Germany
3University Hospital Bonn, Institute of Pathology, 53105 Bonn, Germany
4University Hospital Bonn, Department of Otorhinolaryngology/Head and Neck Surgery, 53105 Bonn, Germany
Jörg Ellinger, email: [email protected]
Keywords: mitochondrial complex III, UQCRFS1, UQCRC1, biomarker, renal cell carcinoma
Received: September 30, 2016 Accepted: October 29, 2016 Published: November 10, 2016
Mitochondrial dysfunction is common in cancer, and the mitochondrial electron transport chain is often affected in carcinogenesis. So far, few is known about the expression of the mitochondrial complex III (ubiquinol-cytochrome c reductase complex) subunits in clear cell renal cell carcinoma (ccRCC). In this study, the NextBio database was used to determine an expression profile of the mitochondrial complex III subunits based on published microarray studies. We observed that five out of 11 subunits of the complex III were downregulated in at least three microarray studies. The decreased mRNA expression level of UQCRFS1 and UQCRC1 in ccRCC was confirmed using PCR. Low mRNA levels UQCRC1 were also correlated with a shorter period of cancer-specific and overall survival. Furthermore, UQCRFS1 and UQCRC1 were also decreased in ccRCC on the protein level as determined using Western blotting and immunohistochemistry. UQCRC1 protein expression was also lower in ccRCC than in papillary and chromophobe subtypes. Analyzing gene expression and DNA methylation in The Cancer Genome Atlas cohort revealed an inverse correlation of gene expression and DNA methylation, suggesting that DNA hypermethylation is regulating the expression of UQCRC1 and UQCRFS1. Taken together, our data implicate that dysregulated UQCRC1 and UQCRFS1 are involved in impaired mitochondrial electron transport chain function.
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