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Researchers from Shanghai Jiaotong University used RNA interference to screen the cancer-testis (CT) gene and identified DUSP21 as a potential therapeutic target for human liver cancer. Related research papers have been accepted and published online in the internationally renowned liver disease journal Hepatology (the latest impact factor 11.665).
Researchers from Shanghai Jiaotong University used RNA interference to screen the cancer-testis (CT) gene and identified DUSP21 as a potential therapeutic target for human liver cancer. Related research papers have been accepted and published online in the internationally renowned liver disease journal Hepatology (the latest impact factor 11.665).
Professors Ze-Guang Han and Dr. Qing Deng of Shanghai Jiaotong University School of Medicine are co-corresponding authors of this paper. Professor Han Zeguang is a Distinguished Professor of the Yangtze River Scholars Award Program of the Ministry of Education and the chief scientist of the “973†project of the Ministry of Science and Technology. The main research direction is the molecular genetics of tumor (liver cancer). Published more than 80 papers in international journals such as Nature and Nature Genetics.
Cancer / Testis Antigen (CTA) is a class of tumor-associated antigens with specific expression patterns. CT gene is specifically expressed in germ cells of normal testis tissues and cancer cells of many different tissue types. It is not expressed in other normal tissues or the expression level is low, and there is an antigenic immune response in cancer patients. Ideal cancer treatment molecule. 96 CT antigens have been found, which are encoded by 15 gene families and 31 genes.
Recently, cell-based RNA interference (RNAi) screening has proven to be a powerful method to identify potential therapeutic targets. In this article, the researchers tried to find some new CT antigens that can be used as potential therapeutic targets for human liver cancer. They analyzed the 179 potential CT genes on the X chromosome by bioinformatics analysis of gene expression profiles. Subsequently, RNAi was used to screen these potential CT genes, and nine necessary CT genes to maintain the survival of liver cancer cell lines Focus and PLC / PRF / 5 were identified.
The researchers found that among these 9 genes, DUSP21, which is physiologically restricted to testis expression and responsible for encoding a bispecific phosphatase, was up-regulated in 39 of 118 human liver cancer samples. Ectopic expression of DUSP21 has no significant effect on the proliferation of hepatoma cells and the formation of cell colonies. But silencing DUSP21 can significantly inhibit cell proliferation, colony formation and tumorigenicity of liver cancer cells in vivo.
When the researchers gave adenovirus-mediated RNAi and atelocollagen / siRNA mixture to interfere with endogenous DUSP21, it was confirmed that it can significantly inhibit xenograft liver cancer tumors in mice. Further investigation revealed that DUSP21 inhibition can lead to G1 phase cell cycle arrest, cell senescence, and changes in the expression of certain factors that play a role in the cell cycle and / or cell senescence. In addition, the researchers confirmed that the inhibition of DUSP21 in liver cancer is through the activation of p38 MAPK to exert anti-proliferative effects.
These results indicate that DUSP21 plays an important role in maintaining the proliferation of liver cancer cells, so it may be a potential therapeutic target for liver cancer.
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