UBE2T mediates SORBS3 ubiquitination to enhance IL‐6/STAT3 signaling and promote lung adenocarcinoma progression

Abstract

AbstractUBE2T is an oncogene in varying tumors, including lung adenocarcinoma (LUAD). SORBS3 is an important signaling regulatory protein that plays a crucial role in many cancers. This study aimed to investigate whether UBE2T promoted LUAD development by mediating the ubiquitination of SORBS3 and further explore its mechanism. Bioinformatics analysis was conducted to examine the expression of SORBS3 in LUAD tissues. Cell Counting Kit‐8, Transwell, and flow cytometry were employed to analyze the cellular functions of SORBS3. Co‐immunoprecipitation and ubiquitination analysis were employed to observe the correlation between UBE2T and SORBS3. In vitro and in vivo experiments verified the role of UBE2T in mediating SORBS3 ubiquitination to enhance interleukin‐6/signal transducer and activator of transcription 3 (IL‐6/STAT3) signaling and promote LUAD development. We observed significant downregulation of SORBS3 in LUAD tissues and cells. Furthermore, SORBS3 inhibited the proliferation, migration, and invasion of LUAD cells, while facilitating apoptosis in vitro. UBE2T enhanced IL‐6/STAT3 signaling by mediating ubiquitination and degradation of SORBS3, thereby promoting LUAD progression. Additionally, this mechanism was further validated in the xenograft animal model in vivo. This study confirmed that UBE2T‐mediated SORBS3 ubiquitination enhanced IL‐6/STAT3 signaling and promoted LUAD progression, providing a novel therapeutic target for LUAD.