Upregulation of SDHA inhibited proliferation, migration, and invasion of clear cell renal cell carcinoma cells via inactivation of the Wnt/β-catenin pathway.

Abstract

Clear cell renal cell carcinoma (ccRCC) is a common genitourinary malignancy with high mortality. Recent findings suggest that the succinate dehydrogenase complex subunit A (SDHA) is lowly expressed in many types of cancers and involved in tumorigenesis. However, the potential regulatory roles and molecular mechanisms by which SDHA affects the development and progression of ccRCC remain largely unknown. In this study, our results showed that there was significant downregulation of SDHA in ccRCC tissue relative to corresponding non-cancerous tissue, and low expression of SDHA was associated with Fuhrman pathological grade, tumor size, TNM stage, metastasis, and poor prognosis in ccRCC patients. Moreover, overexpression of SDHA inhibited the proliferation, invasion, and migration capacities of ccRCC cells. Mechanistically, SDHA impeded the proliferation and metastasis of ccRCC cells by inactivation of the Wnt/β-catenin pathway. In vivo experiments, SDHA suppressed ccRCC growth in a nude mouse model. In conclusion, our study results indicated that SDHA may act as a new molecular marker for judging the occurrence and development of ccRCC and serve as a therapeutic target for the treatment of human ccRCC.