title: 17β-Hydroxysteroid dehydrogenase type 10 predicts survival of patients with colorectal cancer and affects mitochondrial DNA content.
abstract: Mitochondrial energy production is reduced in tumor cells, and altered mitochondrial respiration contributes to tumor progression. Synthesis of proteins coded by mitochondrial DNA (mtDNA) requires the correct processing of long polycistronic precursor RNA molecules. Mitochondrial RNase P, composed of three different proteins (MRPP1, HSD10, and MRPP3), is necessary for correct RNA processing. Here we analyzed the role of RNase P proteins in colorectal cancer. High HSD10 expression was found in 28%; high MRPP1 expression in 40% of colorectal cancers, respectively. Expression of both proteins was not significantly associated with clinicopathological parameters. Survival analysis revealed that loss of HSD10 expression is associated with poor prognosis. Cox regression demonstrated that patients with high HSD10 tumors are at lower risk. High HSD10 expression was significantly associated with high mtDNA content in tumor tissue. A causal effect of HSD10 overexpression or knock down with increased or reduced mtDNA levels, respectively, was confirmed in tumor cell lines. Our data suggest that HSD10 plays a role in alterations of energy metabolism by regulating mtDNA content in colorectal carcinomas, and HSD10 protein analysis may be of prognostic value.
authors.affiliation: Division of Human Genetics, Medical University Innsbruck, Peter Mayr Straße 1, 6020 Innsbruck, Austria. Electronic address: Albert.Amberger@i-med.ac.at.
authors.forename: Albert
authors.initials: A
authors.lastname: Amberger
authors.affiliation: Division of Human Genetics, Medical University Innsbruck, Peter Mayr Straße 1, 6020 Innsbruck, Austria.
authors.forename: Andrea J
authors.initials: AJ
authors.lastname: Deutschmann
authors.affiliation: Division of Human Genetics, Medical University Innsbruck, Peter Mayr Straße 1, 6020 Innsbruck, Austria.
authors.forename: Pia
authors.initials: P
authors.lastname: Traunfellner
authors.affiliation: Institute of General Pathology, Medical University Innsbruck, Müllerstraße 44, 6020 Innsbruck, Austria.
authors.forename: Patrizia
authors.initials: P
authors.lastname: Moser
authors.affiliation: Laura-Bassi Centre of Expertise-THERAPEP, Research Program for Receptor Biochemistry and Tumor Metabolism, Department of Pediatrics, Paracelsus Medical University Salzburg, Müllner Hauptstraße 48, 5020 Salzburg, Austria.
authors.forename: René G
authors.initials: RG
authors.lastname: Feichtinger
authors.affiliation: Laura-Bassi Centre of Expertise-THERAPEP, Research Program for Receptor Biochemistry and Tumor Metabolism, Department of Pediatrics, Paracelsus Medical University Salzburg, Müllner Hauptstraße 48, 5020 Salzburg, Austria.
authors.forename: Barbara
authors.initials: B
authors.lastname: Kofler
authors.affiliation: Division of Human Genetics, Medical University Innsbruck, Peter Mayr Straße 1, 6020 Innsbruck, Austria. Electronic address: Johannes.Zschocke@i-med.ac.at.
authors.forename: Johannes
authors.initials: J
authors.lastname: Zschocke
mesh_terms: D015094:3-Hydroxyacyl CoA Dehydrogenases / Q000096:biosynthesis* / Q000235:genetics; D000368:Aged; D045744:Cell Line, Tumor; D015179:Colorectal Neoplasms / Q000201:enzymology* / Q000235:genetics*; D004272:DNA, Mitochondrial / Q000235:genetics / Q000378:metabolism*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011379:Prognosis
chemical_list: D004272:DNA, Mitochondrial; D015094:3-Hydroxyacyl CoA Dehydrogenases; C108634:HSD17B10 protein, human
keywords: 17β-Hydroxysteroid dehydrogenase type 10; Colorectal cancer; Mitochondrial DNA; Prognostic marker; Survival