HOGA1 Suppresses Renal Cell Carcinoma Growth via Inhibiting the Wnt/β-Catenin Signalling Pathway

Abstract

Changes in hydroxyproline metabolism are reported to promote tumorigenesis. HOGA1 is a useful marker for diagnosing primary hyperoxaluria 3, catalysing the final step of mitochondrial hydroxyproline metabolism from 4-hydroxy-2-oxoglutarate (HOG) to glyoxylate and pyruvate; however, its specific mechanism in RCC remains unclear. This study investigated the role of HOGA1 in the pathogenesis of ccRCC. The results showed that HOGA1 was decreased significantly in tumour tissues, with this low expression associated with a poor prognosis in patients with ccRCC. QTL mapping showed that Hoga1 was cis-regulated. Gene enrichment analyses showed that Hoga1 co-expressed genes were enriched in the Wnt/β-catenin signalling pathway. Furthermore, in vitro and in vivo assays demonstrated that HOGA1 significantly inhibited the proliferation, invasion and migration of renal carcinoma cells via the Wnt/β-catenin–c-Myc/CyclinD1 axis, probably via regulating the level of HOG. In conclusion, this study demonstrates that HOGA1 has a tumour suppressor role by inhibiting the Wnt/β-catenin signalling pathway. This finding provides new insights into the function of HOGA1 in ccRCC.