Mitochondrial UQCRB as a new molecular prognostic biomarker of human colorectal cancer

ABSTRACT

Ubiquinol cytochrome c reductase binding protein (UQCRB) is important for mitochondrial complex III stability, electron transport, cellular oxygen sensing and angiogenesis. However, its potential as a prognostic marker in colorectal cancer (CRC) remains unclear. The aim of this study was to determine whether UQCRB can be used as a diagnostic molecular marker for CRC. The correlation between the expression of three genes (UQCRB, UQCRFS1 and MT-CYB) in the mitochondrial respiratory chain complex III and clinico-pathological features was determined. Compared to non-tumor tissues, UQCRB gene expression was upregulated in CRC tissues. Gene and protein expression of the genes were positively correlated. Copy number variation (CNV) differences in UQCRB were observed in CRC tissues (1.32-fold) compared to non-tumor tissues. The CNV of UQCRB in CRC tissues increased proportionally with gene expression and clinical stage. Single-nucleotide polymorphisms in the 3′-untranslated region of UQCRB (rs7836698 and rs10504961) were investigated, and the rs7836698 polymorphism was associated with CRC clinical stage. DNA methylation of the UQCRB promoter revealed that most CRC patients had high methylation levels (12/15 patients) in CRC tissues compared to non-tumor tissues. UQCRB overexpression and CNV gain were correlated with specific CRC clinico-pathological features, indicating clinical significance as a prognostic predictor in CRC. Gene structural factors may be more important than gene transcription repression factors with respect to DNA methylation in UQCRB overexpression. Our results provide novel insights into the critical role of UQCRB in regulating CRC, supporting UQCRB as a new candidate for the development of diagnostics for CRC patients.