| Hepatocellular cancer (HCC) is one of the most common and most malignant tumors in the world, ranking the fifth high incidence of malignant tumors and third place of cancer-related death globally. In recent decades, some of the patients have long term survival through early diagnosis and comprehensive therapy. However, in most cases, the prognosis of HCC has not been ameliorated significantly, and recurrence and metastasis of tumor have been the biggest barrier for further improvement of treatment. Therefore, more genes and proteins connected with HCC are still urgently to be investigated, to achieve better prognosis and longer survival.Heat shock proteins (HSPs) are a group of proteins initially induced by heat. As the studies went deeper, the same response had also been observed in HSPs exposed to other environmental and metabolic stimulations such as hypoxia, hyperoxia, anoxia, UV exposure, mechanical injury, etc. In addition, they were found in cells under normal conditions too. Previous studies have revealed that HSPs are a group of ubiquitous proteins in both prokaryotic and eukaryotic cells. They have dual functions: the intracellular HSPs have cytoprotective and antiapoptotic functions, such as ensuring the folding of proteins into correct tertiary structure, transporting proteins across the membranes, and incorporating polypeptides into intracellular membranes, which known as " molecular chaperone"; the extracellular HSPs have some immunogenic functions, through the chaperoning of antigenic peptides.Since their molecular chaperone functions are so important in regulating cellular homeostasis and promoting cell survival, HSPs have been reported to participate in the progression of many diseases such as autoimmune diseases, and neoplastic processes. As the overexpression of HSP27,70,90were detected in various carcinomas comparing with corresponding normal tissues, the relationship between HSPs and cancer has been paid attention. Following studies have not only focused on the relationship between HSPs expression profiles and the clinical indicators and prognosis such as disease classification, invasion, metastasis, therapeutic resistance, etc, but also revealed the function of HSPs in the carcinogenesis. Hsp40, also known as DnaJ, is one of the subfamilies of Heat shock protein family. DnaJ/Hsp40proteins act as a co-chaperone by binding to the chaperone Hsp70through their J domain and stimulating the ATP hydrolysis to help the protein translation, folding, unfolding, translocation, and degradation. They are implicated in various human diseases, such as neurodegenerative disorders, cancers, etc. In this study, we cloned and identified a new gene, DnaJ (Hsp40) homolog, subfamily C, member25(DNAJC25), which locates in cytoplasm. Real-time PCR revealed that expression of DNAJC25was particularly high in liver and it was down-regulated in the hepatocellular carcinoma (HCC) comparing with the adjacent normal tissues. Overexpression of DNAJC25led to an inhibition of colony growth both in quantity and size. Flow cytometry analysis indicated that DNAJC25also significantly increased cell apoptosis. Our data thus indicated that DNAJC25might play an important role in the hepatocellular carcinogenesis, and should be further studied as a potential candidate of tumor suppressor. |
PDF Full Text Request