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

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

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.

Keywords: EMT; LUAD; UBE2V2; apoptosis and proliferation; bioinformatic.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma of Lung* / enzymology
  • Adenocarcinoma of Lung* / pathology
  • Cell Proliferation
  • Humans
  • Lung / pathology
  • Lung Neoplasms* / enzymology
  • Lung Neoplasms* / pathology
  • Prognosis
  • Ubiquitin-Conjugating Enzymes* / metabolism

Substances

  • UBE2V2 protein, human
  • Ubiquitin-Conjugating Enzymes