UBE4B promotes the development of lung adenocarcinoma by enhancing proliferation, migration and glycolysis via PP2A/AKT signaling.

Song Wu, Linlin Xie, Shaofei Cheng, Zhengyang Fan, Hongyang Sang, QianPing Li

Pathology, research and practice 2022 Apr

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This study was designed to explore the function of UBE4B in the development of lung adenocarcinoma (LUAD) and the role of PP2A/AKT in this process. Bioinformatics analysis, qRT-PCR, western blot, and immunohistochemistry were used to assess the gene expression in clinical samples, human LUAD database, human LUAD tissue microarrays, LUAD cells, and tumor xenograft model, respectively. The UBE4B overexpression and shRNA vector was constructed and transfected into LUAD cells, and the cell viability, migration, lactate production, and glycolysis were detected. The interaction between UBE4B and PP2A was assessed by CoIP and ubiquitination assay. The enhanced UBE4B expression is confirmed in LUAD datasets, clinical samples, human LUAD tissue microarrays and LUAD cells. UBE4B is positively associated with the proliferation, migration, lactate production, and glycolysis in LUAD cells, and UBE4B elevated proliferation, migration, lactate production, and glycolysis are abolished by PP2A overexpression. Mechanistically, UBE4B ubiquitinates PP2A and induces the activation of AKT. In conclusion, UBE4B act as an oncogene in the development of LUAD through PP2A/AKT signaling. UBE4B could be a new target for diagnosis and treatment of lung adenocarcinoma. Copyright © 2022. Published by Elsevier GmbH.

Citation

Song Wu, Linlin Xie, Shaofei Cheng, Zhengyang Fan, Hongyang Sang, QianPing Li. UBE4B promotes the development of lung adenocarcinoma by enhancing proliferation, migration and glycolysis via PP2A/AKT signaling. Pathology, research and practice. 2022 Apr;232:153762