In this study, we not only clarified the mechanism by which HNK inhibits the glycolysis of cancer cells but also identified E3 ubiquitin ligase in the ubiquitination process of HIF-1α; however, the mechanism through which HNK promotes the ubiquitination degradation of HIF-1α via UFL1 and BRE1B remains to be further studied—this will help better understand the role of HNK in the energy metabolism of tumor cells. The gene discussed is RNF40; the disease is neoplasm.