ena-STUDY-COS (Center for Organismal Studies)-22-04-2020-17:23:44:284-68
Bulk RNA-seq analysis upon siRNA USP42 in colorectal cancer cells
Colorectal cancer progression occurs through the acquisition of selective genetic alterations, including in components of the Wnt pathway and p53 signalling. In this study we uncover that deubiquitinase USP42, beyond regulating p53 stability, antagonizes R-spondin by protecting ZNRF3/RNF43 from ubiquitin-dependent clearance. This inhibits autocrine WNT signaling, most notably in colon cancer cells and mouse intestinal organoids.  In this RNA-seq, we performed a knockdown of USP42 in HCT116 colorectal cancer cells and afterwards bulk-RNA sequencing. Among the upregulated enriched clusters upon siUSP42, we found EMT, ubiquitination, Wnt signaling or DNA repair and cell cycle, thereby increasing cancer cell survival and malignancy properties. Furthermore, p53 target gene signature was down regulated.
Colorectal cancer progression occurs through the acquisition of selective genetic alterations, including in components of the Wnt pathway and p53 signalling. In this study we uncover that deubiquitinase USP42, beyond regulating p53 stability, antagonizes R-spondin by protecting ZNRF3/RNF43 from ubiquitin-dependent clearance. This inhibits autocrine WNT signaling, most notably in colon cancer cells and mouse intestinal organoids.  In this RNA-seq, we performed a knockdown of USP42 in HCT116 colorectal cancer cells and afterwards bulk-RNA sequencing. Among the upregulated enriched clusters upon siUSP42, we found EMT, ubiquitination, Wnt signaling or DNA repair and cell cycle, thereby increasing cancer cell survival and malignancy properties. Furthermore, p53 target gene signature was down regulated.