Abstract
Abstract Hepatocellular carcinoma (HCC) has been the leading cause of death in Taiwan over the years. Aging progression has been regarded as positively correlated with cancer occurrence, owing to the accumulation of mutations. Hence, uncovering the effect of genes on extending longevity becomes a pivotal concept understanding the cancer formation and even developing cancer therapy. Recently, we reported that reduced neuronal expression of ribose-5-phosphate isomerase (rpi) extends lifespan and ameliorates polyglutamine toxicity in Drosophila. Following, we examined the possible role of ribose-5-phosphate isomerase (rpi) gene in cancer formation. We found increased expression of human ribose-5-phosphate isomerase A (hRPIA) in the malignant tissues. The liver cancer tissue array showed that hRPIA protein expression was significantly elevated as the cells entered the malignant stages, suggesting that hRPIA plays a role in liver tumor progression. Furthermore, increased hRPIA expression results in a significant enhancement in the cell proliferation, enhanced colony formation, and promoted cell migration in vitro and in vivo in Hep3B and PLC/PRF/5 liver cancer cells and in HEK293 non-cancer cell lines. Further mechanism study reveals that hRPIA may modulate mitogen-activated protein kinase (MAPK) signaling activity in the regulation of tumor cell growth and progression. In addition, hRPIA overexpression is associated with reduced E-cadherin expression and increased Vimentin expression which may promote cell migration ability. Our study demonstrates an ideal example of the lifespan promotion effect by the reduced expression of ribose-5-phosphate isomerase to become an anti-cancer strategy. The development of hRPIA inhibitor drugs may be useful not only in cancer therapy and neurodegeneration, and also promote healthy longevity.