Digital Public Defence: Zhiru Wang
MD Zhiru Wang at Institute of Clinical Medicine will be defending the thesis “Ubiquitin specific protease7 as a potential therapeutic target for gastric cancer” for the degree of PhD (Philosophiae Doctor).
The public defence will be held as a video conference over Zoom.
The defence will follow regular procedure as far as possible, hence it will be open to the public and the audience can ask ex auditorio questions when invited to do so.
Due to copyright reasons, an electronic copy of the thesis must be ordered from the faculty. In order for the faculty to have time to process the order, it must be received by the faculty no later than 2 days prior to the public defence. Orders received later than 2 days before the defence will not be processed. Inquiries regarding the thesis after the public defence must be addressed to the candidate.
Digital Trial Lecture – time and place
- First opponent: Professor Xiaolin Zi, University of California, Irvine, USA
- Second opponent: Professor Yaohe Wang, Queen Mary University of London, UK
- Third member and chair of the evaluation committee: Associate Professor Marianne Klemp, University of Oslo
Chair of the Defence
Professor II Anne Hansen Ree, University of Oslo
Professor Ole Andreassen, University of Oslo
Gastric cancer (GC) is a challenging disease because the outcome regarding postoperative mortality and long-term survival remains unsatisfactory. The hope to improve the survival percentage of patients with GC rests on the further exploration and the better understanding of the pathogenesis and biological characteristics of GC. As a deubiquitinating enzyme, Ubiquitin specific protease 7 (USP7) is involved in the regulation of several oncogenic pathways and related to various cancer types. Inhibition of USP7 has represented as a promising pharmaceutical strategy in treatment of several human malignancies. However, the potential that USP7 can be used as a therapeutic target for GC treatment remains unknown. Therefore, in this project we have investigated the expression of USP7 in GC and what it follows USP7 inhibition both in vitro and in vivo.
Overexpression of USP7 in GC tissues is correlated with the clinical pathology of GC patients. Pharmacological and genetic abrogation of USP7 suppresses the proliferation of gastric cancer cell line both in vitro and in vivo. Besides, USP7 inhibitor can also down-regulate cancer causing protein PD-L1 expression to enhance anti-tumor immune response. Furthermore, bioinformatics analysis and results show that USP7 physically interacts with and functionally stabilizes cancer causing protein LSD1 in androgen dependent manner. Thus, the USP7-LSD1 axis might be critical for GC tumorigenesis, and targeting this axis could be a potential therapeutic strategy against GC.
In summary, for the first time we explore the function of USP7 in GC and demonstrate a direct physical and functional interaction between USP7 and PD-L1. Meanwhile, we study the regulation mechanism of USP7 on LSD1 in GC. Our exploration provides a new theoretical viewpoint for elucidating the molecular mechanism of malignant proliferation of GC, and offers a strong support for the USP7-targeted-anti-cancer drug development.
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