Department of Thoracic Surgery, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Pudong New District, Shanghai 200233, China.
Department of foundation courses, AnHui Medical College, Hefei 230000, China.
Pathol Res Pract. 2022 Apr;232:153762. doi: 10.1016/j.prp.2022.153762. Epub 2022 Jan 7.
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.
这项研究旨在探索 UBE4B 在肺腺癌（LUAD）发展中的作用，以及 PP2A/AKT 在这一过程中的作用。通过生物信息学分析、qRT-PCR、western blot 和免疫组织化学，分别评估了临床样本、人类 LUAD 数据库、人类 LUAD 组织微阵列、LUAD 细胞和肿瘤异种移植模型中的基因表达情况。构建了 UBE4B 过表达和 shRNA 载体，并转染至 LUAD 细胞，检测细胞活力、迁移、乳酸生成和糖酵解。通过 CoIP 和泛素化测定评估 UBE4B 与 PP2A 之间的相互作用。UBE4B 在 LUAD 数据集、临床样本、人类 LUAD 组织微阵列和 LUAD 细胞中均有增强表达。UBE4B 与 LUAD 细胞中的增殖、迁移、乳酸生成和糖酵解呈正相关，而 PP2A 的过表达可消除 UBE4B 引起的增殖、迁移、乳酸生成和糖酵解增强。在机制上，UBE4B 泛素化 PP2A 并诱导 AKT 的激活。总之，UBE4B 通过 PP2A/AKT 信号通路在 LUAD 的发展中起癌基因作用。UBE4B 可能成为诊断和治疗肺腺癌的新靶点。
