IGF2BP2-modified UBE2D1 interacts with Smad2/3 to promote the progression of breast cancer.

Abstract

Recent studies have suggested that ubiquitin-conjugating enzyme E2D1 (UBE2D1) is involved in tumor progression. In this study, we found that UBE2D1 expression was upregulated in breast cancer (BC) and was related to the prognosis of BC patients. Through in vitro and in vivo experiments, we demonstrated the aberrant expression of UBE2D1 promoted the proliferation and migration of BC cells, and the IGF2BP2-mediated N6-methyladenosine (m6A) modification increased the stability of UBE2D1 mRNA. Mechanistically, UBE2D1 expression regulated the activity of TGF-β signaling through modulating the expression and the phosphorylation level of Smad2/3. Furthermore, UBE2D1 directly bound to Smad2/3 and affected the subsequent binding of Smad2 and Smad3, which is a necessary step for TGF-β signaling activation. Thus, our study reveals a pro-oncogenic role of UBE2D1 in the progression of BC and may provide novel strategies for BC treatment.

• Authors: Xiao-Qing Guan, Xiao-Ning Yuan, Kai-Xiang Feng, You-Cheng Shao, Qin Liu, Ze-Lin Yang, Yan-Yan Chen, Jin Deng, Mei-Shun Hu, Jun Li, Yi-Hao Tian, Meng-Fei Chu, Jing-Wei Zhang, Lei Wei
• Journal: American journal of cancer research (Am J Cancer Res) Vol. 13 Issue 7 Pg. 2948-2968 ( 2023) ISSN: 2156-6976 [Print] United States
• PMID: 37560007 (Publication Type: Journal Article)
• Copyright: AJCR Copyright © 2023.