Knockdown of ubiquitin-like modifier-activating enzyme 2 promotes apoptosis of clear cell renal cell carcinoma cells

Zhang, Guoxi; Zou, Junrong; Shi, Jinglin; Bian, Qian; Qiu, Kaiyang; Liu, Quanliang; Xie, Ting; He, Zhihua; Xu, Hui; Liao, Yijie; Wu, Yuting; Li, Yanmin; Xiao, Guancheng; Yuan, Yuanhu; Xiao, Ran; Wu, Gengqing; Zou, Xin

doi:10.1038/s41419-021-04347-7

Cited by 5 publications

(4 citation statements)

References 31 publications

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“…Database analysis revealed that it was expressed in the cytoplasm predicted from UniProt 24 . UBA2-KD promotes the apoptosis of clear cell renal cell carcinoma cells 25 . Apoptosis-related phenotypes are discussed in this study, as apoptosis and autophagy are related to cancer 26 .…”

Section: Resultsmentioning

confidence: 99%

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IGF2BP3 Regulates TMA7-mediated Autophagy and Cisplatin Resistance in Laryngeal Cancer via m6A RNA Methylation

Yang¹,

Yan²,

Qu³

et al. 2023

Int. J. Biol. Sci.

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Translation machinery associated 7 homolog (TMA7) is closely related to proliferation-related diseases. However, the function and regulatory mechanism of TMA7 in laryngeal squamous cell carcinoma (LSCC) remain unclear. The present study aimed to investigate the effect of TMA7 on the occurrence and development of LSCC and to study the mechanism of TMA7. TMA7 is upregulated in LSCC tissues and associated with poor prognosis. After TMA7 downregulation, the autophagy level was increased, and the proliferation, migration, and invasion of LSCC cells were inhibited. The m6A methylated reader IGF2BP3 enhanced the stability of TMA7 and reduced the level of autophagy. TMA7 interacted directly with UBA2. Furthermore, the activation of the IGF2BP3-regulated TMA7-UBA2-PI3K pathway is the primary mechanism by which TMA7 inhibits autophagy and promotes the progression of LSCC. The current study revealed that IGF2BP3-mediated TMA7 m6A modification promotes LSCC progression and cisplatin-resistance through UBA2-PI3K pathway, providing new insights into the autophagy-related mechanism, potential biomarkers, and therapeutic targets for LSCC.

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Section: Resultsmentioning

confidence: 99%

“…Database analysis revealed that it was expressed in the cytoplasm predicted from UniProt [24]. UBA2-KD promotes the apoptosis of clear cell renal cell carcinoma cells [25].…”

Section: Tma7 Is Associated With Autophagy Of Lscc Cellsmentioning

confidence: 99%

IGF2BP3 Regulates TMA7-mediated Autophagy and Cisplatin Resistance in Laryngeal Cancer via m6A RNA Methylation

Yang¹,

Yan²,

Qu³

et al. 2023

Int. J. Biol. Sci.

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“…In renal cell carcinoma, significantly increased UBA2 expression is related to higher stages and poorer prognosis. Downregulation of UBA2 promoted apoptosis and inhibited proliferation (Zhang et al 2021 ). In small cell lung cells, UBA2 expression is significantly upregulated; however, its knockdown suppresses the migration, invasion, and growth of lung cells and increases their sensitivity to chemotherapeutic drugs cisplatin and etoposide (Liu et al 2015 ).…”

Section: Discussionmentioning

confidence: 99%

SUMOylation of RALY promotes vasculogenic mimicry in glioma cells via the FOXD1/DKK1 pathway

Cao,

Wang,

Wang

et al. 2023

Cell Biol Toxicol

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Human malignant gliomas are the most common and aggressive primary malignant tumors of the human central nervous system. Vasculogenic mimicry (VM), which refers to the formation of a tumor blood supply system independently of endothelial cells, contributes to the malignant progression of glioma. Therefore, VM is considered a potential target for glioma therapy. Accumulated evidence indicates that alterations in SUMOylation, a reversible post-translational modification, are involved in tumorigenesis and progression. In the present study, we found that UBA2 and RALY were upregulated in glioma tissues and cell lines. Downregulation of UBA2 and RALY inhibited the migration, invasion, and VM of glioma cells. RALY can be SUMOylated by conjugation with SUMO1, which is facilitated by the overexpression of UBA2. The SUMOylation of RALY increases its stability, which in turn increases its expression as well as its promoting effect on FOXD1 mRNA. The overexpression of FOXD1 promotes DKK1 transcription by activating its promoter, thereby promoting glioma cell migration, invasion, and VM. Remarkably, the combined knockdown of UBA2, RALY, and FOXD1 resulted in the smallest tumor volumes and the longest survivals of nude mice in vivo. UBA2/RALY/FOXD1/DKK1 axis may play crucial roles in regulating VM in glioma, which may contribute to the development of potential strategies for the treatment of gliomas.

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“…Moreover, ubiquitin-conjugating enzyme E2T has been reported to play a critical role in ccRCC progression and may be a potential therapeutic target for ccRCC [ 17 ]. Recently, ubiquitin-like modifier-activating enzyme 2, an important member of the SUMO modification system, was found to promote the cell growth of ccRCC [ 18 ]. Considering the ambiguous relationship between ubiquitination and prognosis of ccRCC, developing a lncRNA signature-based model has an important clinical value in the prognosis of ccRCC.…”

Section: Introductionmentioning

confidence: 99%

Construction of an individualized clinical prognostic index based on ubiquitination-associated lncRNA in clear cell renal cell carcinoma patients

Liu

Sun

et al. 2022

World J Surg Onc

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Background ccRCC is considered as the main subtype of RCC, which accounted for sixth deadliest cancer worldwide. Recently, ubiquitination has been reported to be closely involved in the progression of tumore. The purpose of this study was to identify the ubiquitination-associated genes and co-expressed lncRNAs on the prognosis of clear cell renal cell carcinoma (ccRCC) patients. Methods and patients We downloaded 530 cases and the corresponding transcriptome profiling from The Cancer Genome Atlas (TCGA) database. We distinguished mRNA and lncRNA expression data from the transcriptome profiling and then extracted the expression of mRNAs that regulate protein ubiquitination. We obtained lncRNAs associated with protein ubiquitination regulation from the lncRNA data by gene co-expression analysis. Cox regression analysis of survival time, survival status, and lncRNA expression level was carried out, and a prognostic index (PI) was constructed. Results The PI was established based on 8 prognostic lncRNAs that regulate protein ubiquitination and distinguish the high-risk group patients from all patients. Multivariate analysis indicated that this PI was an individualized clinical prognostic factor for patients with ccRCC. Regarding clinical characteristics, a ubiquitination-associated clinical-prognostic index (UCPI), containing 8 ubiquitination-related lncRNAs and age, was established and tested with AUC of 0.80. Conclusion We established a UCPI containing 8 lncRNAs related to protein ubiquitination. This UCPI may become an appropriate model to predict the prognosis in ccRCC patients and guide clinicians to adjust the follow-up regimen.

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Knockdown of ubiquitin-like modifier-activating enzyme 2 promotes apoptosis of clear cell renal cell carcinoma cells

Cited by 5 publications

References 31 publications

IGF2BP3 Regulates TMA7-mediated Autophagy and Cisplatin Resistance in Laryngeal Cancer via m6A RNA Methylation

IGF2BP3 Regulates TMA7-mediated Autophagy and Cisplatin Resistance in Laryngeal Cancer via m6A RNA Methylation

SUMOylation of RALY promotes vasculogenic mimicry in glioma cells via the FOXD1/DKK1 pathway

Construction of an individualized clinical prognostic index based on ubiquitination-associated lncRNA in clear cell renal cell carcinoma patients

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