UBE2T/STAT3 Signaling Promotes the Proliferation and Tumorigenesis in Retinoblastoma

UBE2T/STAT3信号促进视网膜母细胞瘤的增殖和肿瘤发生

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作者:Nuo Xu, Yi Cui, Hong Shi, Guodong Guo, Fengyuan Sun, Tianming Jian, Huiying Rao

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.

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.

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.

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.

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