Abstract
Lung cancer and liver cancer are the first and the second leading cause of cancer related death from cancers worldwide. Our previous studies indicate the expression of ribose 5-phosphate isomerase A (RPIA) is higher in lung tumor and liver tumor biopsy than normal adjacent tissues. RPIA is able to regulate liver cancer cell proliferation and colony formation ability via modulating protein phosphatase 2A (PP2A) and extracellular signal-regulated kinases (ERK) signaling pathway. We want to further examine the role of RPIA in cancer cells. Therefore, we applied immunoprecipitation and LC-MS/MS analysis to identify the proteins interacting with RPIA. We identified stress-70 protein (GRP75), 78 kDa glucose-regulated protein (GRP78) and other six proteins which are potential proteins to interact with RPIA. It still requires more evidences to confirm the interactions between RPIA and these proteins and further studies to figure out which cellular responses would be triggered by the protein-protein interactions, and finally lead to the regulation of cancer cell proliferation. Moreover, we examied whether RPIA is related to the most common tumor suppressor, p53, and found that p53 is upregulated by knockdown of RPIA. Accompanied with the increased expression of p21 and decreased expression of p62, RPIA knockdown might trigger cellular senescence, autophagy and p53 dependent tumor suppressive pathway to attenuate liver cancer and lung cancer cell proliferation. According to our previous researches, knockdown of RPIA causes reduced phospho-GSK3levels and degradation of -catenin in colorectal cancer cells. We showed the similar results using PLC5 liver cancer cells, suggests that Wnt/-catenin signaling pathway may contribute to the regulation of cancer cell proliferation by RPIA. Our studies provide more molecular mechanisms associated with the suppressed cell proliferation by knockdown of RPIA in cancer cells. The information may help the development of RPIA related cancer therapeutic strategies.