[et_pb_section fb_built=”1″ _builder_version=”4.27.4″ _module_preset=”default” custom_padding=”2px|||||” global_colors_info=”{}”][et_pb_row _builder_version=”4.27.4″ _module_preset=”default” custom_padding=”50px|||||” locked=”off” global_colors_info=”{}”][et_pb_column type=”4_4″ _builder_version=”4.27.4″ _module_preset=”default” global_colors_info=”{}”][et_pb_text disabled_on=”off|off|off” _builder_version=”4.27.4″ _module_preset=”default” text_font_size=”16px” custom_margin=”||40px||false|false” global_colors_info=”{}”]<\/p>\n
Sci Rep\u00a0(2026). https:\/\/doi.org\/10.1038\/s41598-026-63336-y<\/span><\/p>\n [\/et_pb_text][et_pb_text _builder_version=”4.27.4″ _module_preset=”default” text_font_size=”16px” custom_margin=”||40px||false|false” global_colors_info=”{}”]<\/p>\n Libetti Debora, Anjum Ruhi, De Angeli Pietro, Monittola Francesca, Crinelli Rita, Sparti Angelo, Magnani Mauro and Bianchi Marzia<\/p>\n [\/et_pb_text][et_pb_text _builder_version=”4.27.4″ _module_preset=”default” locked=”on” global_colors_info=”{}”]<\/p>\n [\/et_pb_text][et_pb_text _builder_version=”4.27.4″ _module_preset=”default” global_colors_info=”{}”]<\/p>\n The polyubiquitin gene\u00a0<\/span>UBC<\/i>\u00a0plays a central role in maintaining ubiquitin pools, under both basal and stress conditions. Although\u00a0<\/span>UBC<\/i> is implicated in cell proliferation and survival, its role in gastric cancer remains largely unexplored. We generated <\/span>UBC<\/i>-knockout (<\/span>UBC <\/i>KO) clones in the 23132\/87 primary gastric cancer cell line via CRISPR\/Cas9 to assess the functional impact of <\/span>UBC<\/i>\u00a0on tumor progression.\u00a0<\/span>UBC<\/i> deletion markedly reduced cellular ubiquitin pools and induced proteasome remodeling, characterized by \u03b25i (PSMB8) upregulation and incorporation into ubiquitin-independent proteasome complexes. Transcriptomic profiling revealed extensive changes in gene expression in <\/span>UBC<\/i>-deficient cells affecting pathways related to cell adhesion, protein homeostasis and cell apoptosis. Notably, <\/span>UBC<\/i>-KO clones exhibited an almost complete abrogation of CD44 expression, a known gastric cancer marker, and the downregulation of pro-metastatic drivers such as <\/span>LGALS4<\/i> and Claudin-1. This transcriptional rewiring translated into reduced proliferation, impaired migratory and invasive capabilities. Our study identifies <\/span>UBC<\/i> as a pivotal regulator of ubiquitin availability that links proteostasis with transcriptional reprogramming regulating tumor aggressiveness. These findings reveal a link between <\/span>UBC<\/i>\u00a0and CD44-mediated gastric cancer progression, highlighting\u00a0<\/span>UBC<\/i> as a novel therapeutic target in this malignancy.<\/span><\/p>\nAbstract<\/h3>\n