Research On Function And Mechanism Of GPRC5A In Colorectal Cancer

Colorectal cancer is the most common primary malignant tumor. It has a high level of malignancy, and is fast growing, with early metastasis and strong invasion. Approximately over 50% of patients experience metastasis to the liver or other organs upon clinical diagnosis. Furthermore, no single molecular target has been identified in the search for a cure for colorectal cancer. Clinical studies have shown that G protein-coupled receptor C5A (Gprc5a) closely associates with the occurrence and development of a variety of tumors. However, how Gprc5a can control the occurrence and development of colorectal cancer is not clear.In this paper, through the analysis of Gprc5a expression levels in colorectal carcinoma specimens, we initially confirmed that the expression of Gprc5a in colorectal cancer tissues is greater than that in corresponding normal tissue. We further determined that with increased Gprc5a expression, tumor malignancy rate also increases. The level of Gprc5a expression was negatively correlated with the survival rate of the patients. Additionally, we found that Gprc5a can regulate the proliferation of colorectal cancer cells, as well as apoptosis and colony forming ability in vitro. In mice, we found that a knockdown of Gprc5a can inhibit the occurrence of tumors and the development of colorectal cancer, leading to a colitis-associated cancer model and promotion of tumor apoptosis. Finally, from the viewpoint of oxidative stress, we confirmed that Gprc5a can regulate the Vavin-1 gene and its product cystamine, which negatively regulates glutathione. We further confirmed that cystamine rescues the cell phenotype due to a down-regulation of Gprc5a, as observed through a recovery experiment. Lastly, from the molecular perspective, we confirmed that Vavin-1 was regulated by Gprc5a through NF-kappa B signaling pathway. In summary, via the NF-B signaling pathway, Gprc5a regulates its downstream Vavin-1 gene, which ultimately gives rise to cystamine, which affects the content of glutathione, which thereby regulates the production of gamma- glutamylcysteine synthetase, which regulates oxidative stress in tumor microenvironments. Therefore, through this pathway Gprc5a regulates and controls the occurrence and development of colorectal cancer.