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Lilian Gu

Poster #033

Beta-Lapachone Suppresses Cancer Proliferation Through Targeting USP22

Mentors: Keqiang Zhang, Associate Research Professor and Yuanyuan Gao, Scientific/Research Fellow

Ubiquitin-specific peptidase 22 (USP22) is a putative cancer stem cell biomarker, which frequently overexpressed, significantly associated with therapy resistance and disease recurrence. USP22 controls gene expression via catalyzing the removal of the mono-ubiquitin moiety from H2B (H2Bub1). We have identified Beta-Lapachone, a plant product with many pharmacological effects including inhibiting topoisomerase I, suppressed USP22 Dub activity. Herein, we find that Beta-Lapachone significantly suppresses the in vitro proliferation of lung cancer cells, A549, colorectal cancer cells, HCT116, and increases H2Bub1. USP22-Knockout A549 cell are more resistant to beta-Lapachone, which indicates the inhibitory effects of Beta-Lapachone may be partially dependent on targeting USP22 in cancer cells. The impact of beta-Lapachone on lung cancer stem cell sphere formation is still ongoing. In summary, the finding indicates Beta-Lapachone represents a potential USP22 inhibitor and expands our understanding of the mechanisms of Beta-Lapachone’s pharmacological effects, broadening its potential application in cancer therapy.