Different hypoxic response of human CAVII and Caenorhabditis elegans homologous genes CAH-3, CAH-4, CAH-5

Abstract

Background/aim: A number of carbonic anhydrase (CA) family proteins have been implicated in cancer. They contribute to the hypoxic microenvironment. CAVII is often downregulated in colorectal carcinoma and it has been associated with increased tumor size, node metastasis, and adverse clinical outcomes. In this study, we aimed to investigate the effect of hypoxia on CAVII protein in human colon cancer and prostate cancer cells. In addition, the regulation of CAH genes in Caenorhabditis elegans was examined. These are homologous to CAVII in humans. Materials and methods: CAVII expression was analyzed in different cell lines such as human colon cancer (SW480 and HT-29), human prostate cancer (PC3 and LNCaP), human hepatocellular carcinoma (Hep3B) and Human umbilical vein endothelial cells (HUVEC). HT-29 and LNCaP cell lines were subjected to a chemical hypoxia model with CoCl2. Real-time PCR was used for CAVII mRNA analysis. Western blot and immunofluorescence (IF) staining were used to detect the CAVII protein. The response of CAH genes was also studied at the mRNA level in a chemical hypoxia model with sodium sulfite in C. elegans. CAVII and CAVII-like genes CAH-3, CAH-4, and CAH-5 were analyzed bioinformatically. Results: We found that CAVII expression decreased under hypoxic conditions in HT-29, but conversely, increased in LNCaP cells at the mRNA and protein level. In the hypoxia model in C. elegans, CAH genes were downregulated. According to bioinformatics analyses, human CAVII was most similar to CAH-3 (98%). Conclusion: The results emphasize the necessity of addressing hypoxic regulation in different cell and organism groups in cancer and healthy conditions for CA family members that change under physiological and pathophysiological conditions. Postgenomic studies are important to better understand the evolution of these ancient enzymes.