UBE2T is upregulated, predicts poor prognosis, and promotes cell proliferation and invasion by promoting epithelial-mesenchymal transition via inhibiting autophagy in an AKT/mTOR dependent manner in ovarian cancer

Huang, Wei; Huang, Hongyan; Xiao, Yuzhen; Wang, Lei; Zhang, Tingting; Fang, Xiaoling; Xia, Xiaomeng

doi:10.1080/15384101.2022.2031426

Cited by 7 publications

(7 citation statements)

References 38 publications

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“…84 Similarly, UBE2T, an oncogene in OC, is upregulated to inhibit autophagy by activating the AKT/ mTOR signaling pathway, which subsequently boosts epithelial-mesenchymal transition. 85 These findings reveal that blocking autophagic cell death accelerates malignant progression in OC. Furthermore, it is reported that OC patients with higher Mfn2 expression show favorable survival than those with lower Mfn2 levels; further mechanistic evaluation unveils that Mfn2 promotes autophagy via activating the AMPK-mediated repression of mTOR and ERK signaling pathways.…”

Section: Tumor Suppressormentioning

confidence: 84%

Role of autophagy and its regulation by noncoding RNAs in ovarian cancer

Feng

Yuan

2023

Exp Biol Med (Maywood)

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Autophagy is a self-digestion process by which misfolded proteins and damaged organelles in eukaryotic cells are degraded to maintain cellular homeostasis. This process is involved in the tumorigenesis, metastasis, and chemoresistance of various tumors such as ovarian cancer (OC). Noncoding RNAs (ncRNAs), mainly including microRNAs, long noncoding RNAs, and circular RNAs, have been extensively investigated in cancer research for their roles in the regulation of autophagy. Recent studies have shown that in OC cells, ncRNAs can modulate the formation of autophagosomes, which affect tumor progression and chemoresistance. An understanding of the role of autophagy in OC progression, treatment, and prognosis is important, and the identification of the regulatory roles of ncRNAs in autophagy leads to intervention strategies for OC therapy. This review summarizes the role of autophagy in OC and discusses the role of ncRNA-mediated autophagy in OC, as an understanding of these roles may contribute to the development of potential therapeutic strategies for this disease.

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Section: Tumor Suppressormentioning

confidence: 84%

Role of autophagy and its regulation by noncoding RNAs in ovarian cancer

Feng

Yuan

2023

Exp Biol Med (Maywood)

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“…Upon UBE2T knockdown, Akt/mTOR inactivation activated autophagy in ovarian cancer (OV) cells, causing UBE2T depletion and inhibiting EMT. UBE2T upregulation could predict poor prognosis and promote the malignant progression of OV (7). UBE2T upregulation also showed a strong correlation with poor OS in OV.…”

Section: Expression Of Ube2t In Cancermentioning

confidence: 85%

“…Ubiquitin-conjugating enzyme E2 T (UBE2T, also known as E2 ubiquitin-conjugating enzyme T, FANCT, PIG50 and HSPC150) belongs to the UBE2 superfamily, which plays a fundamental role in the second step of ubiquitination. Following previous studies that reported that UBE2T was involved in the regulation of DNA repair in Fanconi anaemia (FA), it was recently molecularly identified as a risk factor closely associated with oncogenesis, metastasis, survival and prognosis in human patients or mammal animals with cancer (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11).…”

Section: Introductionmentioning

confidence: 99%

Diverse roles of UBE2T in cancer (Review)

Yan

et al. 2023

Oncol Rep

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As a leading cause of mortalities worldwide, cancer results from accumulation of both genetic and epigenetic alterations. Disruption of epigenetic regulation in cancer, particularly aberrant ubiquitination, has drawn increasing interest in recent years. The present study aimed to review the roles of ubiquitin-conjugating enzyme E2 T (UBE2T) and its associated pathways in the pathogenesis of pan-cancer, and the development of small-molecule modulators to regulate ubiquitination for treatment strategies. The current study comprehensively investigated the expression landscape and functional significance of UBE2T, as well as its correlation with cancer cell sensitivity to chemotherapy/radiotherapy. Multiple levels of evidence suggested that aberrant UBE2T played important roles in pan-cancer. Information was collected from 16 clinical trials on ubiquitin enzymes, and it was found that these molecules had an important role in the ubiquitin-proteasome system. Further studies are necessary to explore their feasibility and effectiveness as diagnostic and prognostic biomarkers, or as up/down-stream and therapeutic targets for cancer treatment.

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“… 8 Further, UBE2T overexpression enhances malignant progression by activating the PI3K-AKT signaling pathway in ovarian cancer, lung adenocarcinoma, breast cancer, renal cell carcinoma, and osteosarcoma. 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.…”

Section: Discussionmentioning

confidence: 98%

“… 8 , 9 In addition to its relevance in FA, UBE2T also has vital roles in the development, progression, and recurrence of various tumors. 10–14 UBE2T facilitates the occurrence and development of ovarian cancer by regulating epithelial–mesenchymal transition (EMT) through the PI3K-AKT pathway. 15 Further, silencing of UBE2T represses lung adenocarcinoma progression by increasing the expression of fibulin 5, 16 and UBE2T can also promote pyrimidine metabolism by enhancing Akt K63-linked ubiquitination, thus contributing to hepatocellular carcinoma (HCC) development.…”

Section: Introductionmentioning

confidence: 99%

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

Wang¹,

Gao²,

Wei³

et al. 2023

DDDT

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Purpose Patients with glioblastoma (GBM) have poor prognosis and limited therapeutic options, largely because of chemoresistance to temozolomide (TMZ) treatment. Ubiquitin conjugating enzyme E2 T (UBE2T) plays a key role in regulating the malignancy of various tumors, including GBM; however, its role in TMZ resistance of GBM has not been elucidated. The purpose of this study was to clarify the role of UBE2T in mediating TMZ resistance and investigate the specific underlying mechanism. Methods Western blotting was used to detect the protein levels of UBE2T and Wnt/β-catenin-related factors. CCK-8, flow cytometry, and colony formation assays were used to examine the effect of UBE2T on TMZ resistance. Wnt/β-catenin signaling pathway activation was inhibited using XAV-939, and a xenograft mouse model was generated to clarify the function of TMZ in vivo. Results UBE2T knockdown sensitized GBM cells to TMZ treatment, whereas UBE2T overexpression promoted TMZ resistance. The specific UBE2T inhibitor, M435-1279, increased the sensitivity of GBM cells to TMZ. Mechanistically, our results demonstrated that UBE2T induces β-catenin nuclear translocation and increases the protein levels of downstream molecules, including survivin and c-Myc. Inhibition of Wnt/β-catenin signaling using XAV-939 blocked TMZ resistance due to UBE2T overexpression in GBM cells. In addition, UBE2T was shown to facilitate TMZ resistance by inducing Wnt/β-catenin signaling pathway activation in a mouse xenograft model. Combined treatment with TMZ and UBE2T inhibitor achieved superior tumor growth suppression relative to TMZ treatment alone. Conclusion Our data reveal a novel role of UBE2T in mediating TMZ resistance of GBM cells via regulating Wnt/β-catenin signaling. These findings indicate that targeting UBE2T has promising potential to overcome TMZ resistance of GBM.

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UBE2T is upregulated, predicts poor prognosis, and promotes cell proliferation and invasion by promoting epithelial-mesenchymal transition via inhibiting autophagy in an AKT/mTOR dependent manner in ovarian cancer

Cited by 7 publications

References 38 publications

Role of autophagy and its regulation by noncoding RNAs in ovarian cancer

Role of autophagy and its regulation by noncoding RNAs in ovarian cancer

Diverse roles of UBE2T in cancer (Review)

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

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