UBE2T/STAT3 Signaling Promotes the Proliferation and Tumorigenesis in Retinoblastoma

Abstract

Purpose The purpose of this paper was to investigate the expression and function of Ubiquitin-conjugating enzyme 2T (UBE2T), a human E2 ubiquitin-conjugating enzyme, in human retinoblastoma. Methods The expression of UBE2T in normal retina and retinoblastoma was analyzed using the Gene Expression Omnibus (GEO) databases, and its expression was immunohistochemically evaluated in 29 retinoblastoma sections and 5 normal retinas. Then CCK-8, flow cytometry, RNA-sequencing analysis, and in vivo assays were performed to explore the exact role of UBE2T in retinoblastoma. Results We found that retinoblastoma showed higher UBE2T expression than normal retina in GEO datasets and tissues. The immunoreactive score of UBE2T ≥4 was associated with group E in IIRC, T2-T4b in pTNM staging, poorly differentiated retinoblastoma, and high-risk histopathological factors. Knockdown of UBE2T reduced the cell viability, increased the apoptosis cells and G0/G1 cells, and inhibited subcutaneous tumor growth in vivo. Mechanistic studies showed that UBE2T knockdown induced down-regulation of phosphorylation of STAT3 and its downstream genes in vitro and in vivo. Rescue assays confirmed that STAT3 signaling pathway was involved in the effect of reduced cell viability, elevated apoptosis cells, and G0/G1 cells mediated by UBE2T knockdown. Conclusions Our data indicate that UBE2T significantly participates in the proliferation of retinoblastoma via the STAT3 signaling pathway, suggesting the potential of UBE2T as a therapeutic target for retinoblastoma treatment.

UBE2L3 expression in human gastric cancer and its clinical significance

“…In recent years, there has been increasing research interest in the role of E2s in tumors. UBE2T, functioning as an E2 enzyme, has been identified as a crucial regulator of tumor advancement in various types of cancer, including gastric cancer (Yu et al 2021 ), hepatocellular carcinoma (Sun et al 2020 ), pancreatic cancer (Jiang et al 2023 ), lung adenocarcinoma (Zhu et al 2021 ), retinoblastoma (Xu et al 2022 ), and glioblastoma (Huang et al 2020 ). Furthermore, Qi et al reported that the overexpression of UbcH5c was linked to a negative prognosis in pancreatic cancer (Qi et al 2022 ).…”

UBE2T Promotes Temozolomide Resistance of Glioblastoma Through Regulating the Wnt/β-Catenin Signaling Pathway

“… 10 , 28–31 UBE2T significantly promotes retinoblastoma tumorigenesis via STAT3 signaling. 32 Notably, UBE2T induces Wnt/β-catenin pathway activation through RACK1 ubiquitination and degradation, resulting in promotion of gastric cancer progression. 13 Further, UBE2T physically binds to and increases the ubiquitination of Mule, which subsequently mediates β-catenin degradation, thereby regulating liver cancer stem cells.…”