title: Systematic expression analysis of the mitochondrial complex III subunits identifies UQCRC1 as biomarker in clear cell renal cell carcinoma.
abstract: 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.
authors.affiliation: University Hospital Bonn, Department of Urology, 53105 Bonn, Germany.
authors.forename: Jörg
authors.initials: J
authors.lastname: Ellinger
authors.affiliation: University Hospital Bonn, Department of Urology, 53105 Bonn, Germany.
authors.forename: Arabella
authors.initials: A
authors.lastname: Gromes
authors.affiliation: University Hospital Bonn, Department of Urology, 53105 Bonn, Germany.
authors.forename: Mirjam
authors.initials: M
authors.lastname: Poss
authors.affiliation: University Hospital Bonn, Department of Urology, 53105 Bonn, Germany.
authors.forename: Maria
authors.initials: M
authors.lastname: Brüggemann
authors.affiliation: University Hospital Bonn, Department of Urology, 53105 Bonn, Germany.
authors.forename: Doris
authors.initials: D
authors.lastname: Schmidt
authors.affiliation: University Hospital Bonn, Department of Anesthesiology and Intensive Care, 53105 Bonn, Germany.
authors.forename: Nadja
authors.initials: N
authors.lastname: Ellinger
authors.affiliation: University Hospital Bonn, Institute of Pathology, 53105 Bonn, Germany.
authors.forename: Yuri
authors.initials: Y
authors.lastname: Tolkach
authors.affiliation: University Hospital Bonn, Institute of Pathology, 53105 Bonn, Germany.|University Hospital Bonn, Department of Otorhinolaryngology/Head and Neck Surgery, 53105 Bonn, Germany.
authors.forename: Dimo
authors.initials: D
authors.lastname: Dietrich
authors.affiliation: University Hospital Bonn, Institute of Pathology, 53105 Bonn, Germany.
authors.forename: Glen
authors.initials: G
authors.lastname: Kristiansen
authors.affiliation: University Hospital Bonn, Department of Urology, 53105 Bonn, Germany.
authors.forename: Stefan C
authors.initials: SC
authors.lastname: Müller
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor; D002292:Carcinoma, Renal Cell / Q000201:enzymology* / Q000235:genetics / Q000401:mortality; D019175:DNA Methylation; D014450:Electron Transport Complex III / Q000235:genetics*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007506:Iron-Sulfur Proteins / Q000235:genetics*; D007680:Kidney Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000401:mortality; D008297:Male; D008875:Middle Aged; D021122:Protein Subunits; D012333:RNA, Messenger / Q000032:analysis
chemical_list: D014408:Biomarkers, Tumor; D007506:Iron-Sulfur Proteins; D021122:Protein Subunits; D012333:RNA, Messenger; C579514:UQCRFS1 protein, human; D014450:Electron Transport Complex III
keywords: UQCRC1; UQCRFS1; biomarker; mitochondrial complex III; renal cell carcinoma