Aryl hydrocarbon receptor nuclear translocator (ARNT) is a transcription factor that has been reported to play a vital role in regulating glycolysis, angiogenesis and apoptosis. Recently, ARNT has been reported to a play role in pancreatic-islet function in type 2 diabetes. However, the role of ARNT in kidney cancer has not yet been investigated. In the present study, ARNT expression was detected in tissues from patients with renal cell carcinoma (RCC) and in RCC cell lines. Oncomine, The Cancer Genome Atlas and cBioPortal were used to investigate the roles of ARNT in RCC. Cell migration and invasion assays were used to explore the molecular mechanisms involved. It was found that ARNT protein expression was elevated both in tissues from patients with clear cell RCC (ccRCC) and in different RCC cell lines. ARNT disruption using siRNA knockdown inhibited the migratory abilities and cell proliferation, potentially by altering the glycolysis pathway , as evidenced by decreased M2 type acetone kinase, 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3 and hexokinase 2 expression. Taken together, the findings in the present study revealed a novel function of ARNT in ccRCC and indicated that ARNT promotes the proliferation and invasion of ccRCC, possibly through changes to the glycolytic pathway.Copyright: © Zhao et al.