Exploring Cul4a-Associated Proteins and the Therapeutic Values of Adenovirus-Mediated Transfer of Cul4a Rnai in Lung Cancer

Cul4A E3 ubiqutin ligase has been implicated to influence cell cycle regulation; genome stability; nuclear excision repair; apoptosis, and histone modification. Earlier studies have shown that the expression of Cul4A is elevated in malignant pleural mesothelioma, breast, and liver cancers. Cul4A is also involved in the ubiquitination and proteolysis of tumor suppressors, such as p53, p21 and p27, which contribute to tumorgenesis and cancer development. In our earlier study, we observed that Cul4A is overexpressed in lung cancer cell lines. Knockdown of the Cul4A expression by shRNA in lung cancer cells resulted in decreased cellular proliferation and growth in lung cancer cell lines and xenografts. Increased sensitivity to gemcitabine chemotherapy drugs was also noted in those Cul4A knockdown lung cancer cells. However, mechanisms by which Cul4A affects chemosensitivity in lung cancer cells remain unknown. Additionally, the establishment of an animal model to proof the future therapeutic values of Cul4A in target therapy is also necessary. In this study, we will (1) study how the expression of Cul4A influences the expression of TGFBI, (2) investigate the genes and proteins that are regulated by Cul4A, (3) elucidate whether Cul4A RNAi can be used as a therapeutic agent for the treatment of lung cancer. This study will be important to the understanding of the functions of Cul4A for the purpose of treatment of lung cancer.

Project ID:PC10108-0680
External Project ID:NSC101-2314-B182-086-MY2