RESUMEN
Ubiquitin specific peptidase-2 (USP2) plays important roles in a myriad of cellular activities through deubiquitinating target proteins and its implications in various diseases, especially cancers, are starting to emerge. Our current understanding on USP2 expression in subjects with hepatocellular carcinoma (HCC) and its roles in the pathogenesis of HCC is limited. In this study, we found that USP2 protein and mRNA levels were significantly dysregulated in HCC tumor (HCC-T) when compared to adjacent non-tumor (HCC-NT) or normal liver tissues from both human and mouse HCC model. Among the USP2 isoforms, USP2b was the predominant isoform in the normal liver and markedly down-regulated in HCC-T tissues in both human and mice. Data from overexpression, chemical inhibition and knockout studies consistently demonstrated that USP2b promoted cell proliferation, colony formation and wound healing in HepG2 and Huh 7 cells. On the other hand, USP2b exhibited proapoptotic and pronecrtotic activities through enhancing bile acid-induced apoptosis and necrosis in both HepG2 and Huh 7 cells. Unbiased proteomic analysis of USP2-knockout (KO) and parental HepG2 cells resulted in identification of USP2-regulated downstream target proteins involved in cell proliferation, apoptosis, and tumorigenesis, including serine/threonine kinase 4 (STK4), epidermal growth factor receptor (EGFR), dipeptidyl peptidase 4 (DPP4) and fatty acid binding protein 1 (FABP1). In conclusion, USP2b expression was dysregulated in subjects with HCC and contributed to the pathogenesis of HCC by promoting cell proliferation and exerting proapoptotic and pronecrotic activities. The findings provide the molecular basis for developing therapies for HCC through modulating USP2b expression or activities.
RESUMEN
The overarching goal of the Rhode Island-IDeA Network of Biomedical Research Excellence (RI-INBRE) is to improve institutional capacity for biomedical research excellence and expand student experiential training opportunities in the State of Rhode Island. RI-INBRE comprises five major core components: The Administrative Core, the Bioinformatics Core, the Centralized Research Core Facility, the Training Core, and the Developmental Research Project Program Core. Since its inception in 2001, RI-INBRE has made significant investments and marked advancements in the biomedical research infrastructure of Rhode Island. RI-INBRE funding has increased the scale and quality of faculty research and engaged undergraduate students, graduate students, and postdoctoral fellows in structured and mentored research training experiences. Over the last 19 years, RI-INBRE has supported 212 faculty researchers and over 533 projects and has provided research-training opportunities for nearly 2,000 students, resulting in 757 publications. Through its student-training program, RI-INBRE has contributed to regional workforce development by engaging students and encouraging them to pursue careers in biomedical fields. Many of these students have been admitted to graduate or medical schools and obtained biomedical industry jobs following graduation. RI-INBRE has been particularly influential in building the research infrastructure at primarily undergraduate institutions, which have seen significant improvements in research quality and output, student training, and research infrastructure.