UBE2V2 通过调节 EMT 促进转移，并且可预测肺腺癌的不良预后。

UBE2V2 promotes metastasis by regulating EMT and predicts a poor prognosis in lung adenocarcinoma.

机构信息

Department of Respiratory Medicine, Affiliated Hospital of Nantong University, Nantong, China.

Department of Thoracic Surgery, Zhongshan Hospital Fudan University, shanghai, China.

出版信息

Cancer Med. 2023 Oct;12(19):19850-19865. doi: 10.1002/cam4.6566. Epub 2023 Sep 27.

DOI:10.1002/cam4.6566

PMID:37755128

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10587983/

Abstract

PURPOSE

As a member of the ubiquitin-conjugating enzyme (E2) family, UBE2V2 demonstrates significant tumorigenicity in many cancers. However, the relationship between UBE2V2 expression and the morbidity of lung adenocarcinoma (LUAD) is still unknown.

METHODS

We detected the mRNA and protein expression of UBE2V2 and analyzed its relationship with clinical parameters as well as survival prognosis based on bioinformatic and immunohistochemistry (IHC) in LUAD. The signaling pathway of UBE2V2 in the development of LUAD was obtained by GSEA. The TIMER database was used to investigate the association between UBE2V2 expression and the level of infiltration of different immune cells. Finally, we explored the effects of UBE2V2 knockdown on the proliferation, apoptosis, and migration of LUAD cells.

RESULTS

The results showed that UBE2V2 was a potential oncogene and might be considered an independent prognostic molecule for LUAD patients based on TCGA prediction (HR: 1.497 p = 0.012) and IHC (HR:1.864 p = 0.044). IHC showed that UBE2V2 was related to the following clinicopathological factors: gender (p = 0.043), stage (p = 0.042), and lymph node metastasis (p = 0.002). Finally, knockdown of UBE2V2 reduced the migration of LUAD cells by regulating EMT-related proteins. Knockdown of UBE2V2 induced LUAD cells to arrest in the G1 phase. Knockdown of UBE2V2 increased LUAD cell apoptosis and decreased proliferation, which might be related to the downregulation of PCNA and upregulation of P53 and ƳH2AX expression. Interestingly, UBE2V2 is negatively correlated with B cells, CD4+ T cells, macrophages, and dendritic cells.

CONCLUSION

UBE2V2 may be a valuable therapeutic target for lung cancer.

摘要

目的

作为泛素结合酶（E2）家族的一员，UBE2V2 在许多癌症中表现出显著的致瘤性。然而，UBE2V2 表达与肺腺癌（LUAD）发病率之间的关系尚不清楚。

方法

我们检测了 UBE2V2 的 mRNA 和蛋白表达，并基于 LUAD 的生物信息学和免疫组织化学（IHC）分析了其与临床参数及生存预后的关系。通过 GSEA 获得 UBE2V2 在 LUAD 发展中的信号通路。使用 TIMER 数据库研究 UBE2V2 表达与不同免疫细胞浸润水平之间的关系。最后，我们探讨了 UBE2V2 敲低对 LUAD 细胞增殖、凋亡和迁移的影响。

结果

结果表明，UBE2V2 是一种潜在的癌基因，根据 TCGA 预测（HR：1.497，p=0.012）和 IHC（HR：1.864，p=0.044），UBE2V2 可能被认为是 LUAD 患者的独立预后分子。IHC 显示，UBE2V2 与以下临床病理因素相关：性别（p=0.043）、分期（p=0.042）和淋巴结转移（p=0.002）。最后，UBE2V2 的敲低通过调节 EMT 相关蛋白减少 LUAD 细胞的迁移。UBE2V2 的敲低使 LUAD 细胞阻滞在 G1 期。UBE2V2 的敲低增加了 LUAD 细胞的凋亡，降低了增殖，这可能与 PCNA 的下调和 P53 和 γH2AX 表达的上调有关。有趣的是，UBE2V2 与 B 细胞、CD4+T 细胞、巨噬细胞和树突状细胞呈负相关。