Butein promotes ubiquitination-mediated survivin degradation inhibits tumor growth and overcomes chemoresistance

Dong, Xin; Liu, Wenbin; Li, Xiaoying; Gan, Yu; Zhou, Li; Li, Wei; Xie, Lihua

doi:10.1038/s41598-022-21839-4

Cited by 16 publications

(12 citation statements)

References 38 publications

(55 reference statements)

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“…FBXL7, an F-box protein that binds to substrates via SKP1-Cullin-1-F-box (SCF) E3 ubiquitin ligase, could enhance polyubiquitylation and degradation of substrates in tumor occurrence and aggression ( Wang et al, 2022 ). Additionally, FBXL7 reduces chemotherapy resistance by promoting the ubiquitination and degradation of survivin ( Dong et al, 2022 ). IDO-targeting PROTAC peptide (IPP), generated and activated from UPS, leads to the activation of effector T cells that could further suppress tumor growth and metastasis ( Zhang C. et al, 2021 ).…”

Section: Discussionmentioning

confidence: 99%

Ubiquitin-proteasome system-based signature to predict the prognosis and drug sensitivity of hepatocellular carcinoma

et al. 2023

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Background: Ubiquitin-proteasome system (UPS) is implicated in cancer occurrence and progression. Targeting UPS is emerging as a promising therapeutic target for cancer treatment. Nevertheless, the clinical significance of UPS in hepatocellular carcinoma (HCC) has not been entirely elucidated.Methods: Differentially expressed UPS genes (DEUPS) were screened from LIHC-TCGA datasets. The least absolute shrinkage and selection operator (LASSO) and stepwise multivariate regression analysis were conducted to establish a UPS-based prognostic risk model. The robustness of the risk model was further validated in HCCDB18, GSE14520, and GSE76427 cohorts. Subsequently, immune features, clinicopathologic characteristics, enrichment pathways, and anti-tumor drug sensitivity of the model were further evaluated. Moreover, a nomogram was established to improve the predictive ability of the risk model.Results: Seven UPS-based signatures (ATG10, FBXL7, IPP, MEX3A, SOCS2, TRIM54, and PSMD9) were developed for the prognostic risk model. Individuals with HCC with high-risk scores presented a more dismal prognosis than those with low-risk scores. Moreover, larger tumor size, advanced TNM stage, and tumor grade were observed in the high-risk group. Additionally, cell cycle, ubiquitin-mediated proteolysis, and DNA repair pathways were intimately linked to the risk score. In addition, obvious immune cell infiltration and sensitive drug response were identified in low-risk patients. Furthermore, both nomogram and risk score showed a significant prognosis-predictive ability.Conclusion: Overall, we established a novel UPS-based prognostic risk model in HCC. Our results will facilitate a deep understanding of the functional role of UPS-based signature in HCC and provide a reliable prediction of clinical outcomes and anti-tumor drug responses for patients with HCC.

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Section: Discussionmentioning

confidence: 99%

Ubiquitin-proteasome system-based signature to predict the prognosis and drug sensitivity of hepatocellular carcinoma

et al. 2023

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“…uncovered that butein can inhibit NPC cells by downregulating survivin through an Akt-Wel CDK1 signal-dependent mechanism. 34 impeding CRC progression. 39 Another crucial regulatory mechanism, the MAPK signaling pathway, exerts control over a wide array of physiological functions.…”

Section: Discussionmentioning

confidence: 99%

“…Its potent antioxidant, anti‐inflammatory and antitumor properties have been demonstrated across a spectrum of human tumors 14 . For instance, Dong et al uncovered that butein can inhibit NPC cells by downregulating survivin through an Akt‐Wel CDK1 signal‐dependent mechanism 34 . Similarly, Yang et al reported that butein induces apoptosis in ovarian cancer cells by activating both exogenous and endogenous pathways 35 .…”

Section: Discussionmentioning

confidence: 99%

Exploring the mechanism underlying the therapeutic effects of butein in colorectal cancer using network pharmacology and single‐cell RNA sequencing data

Lu,

Shan,

Cheng

et al. 2023

The Journal of Gene Medicine

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BackgroundButein has shown substantial potential as a cancer treatment, but its precise mechanism of action in colorectal cancer (CRC) remains unclear. This study aimed to uncover the underlying mechanisms through which butein operates in CRC and to identify potential biomarkers through a comprehensive investigation.MethodsTarget genes associated with butein were sourced from SwissTargetPrediction, CTD, BindingDB and TargetNet. Gene expression data from the GSE38026 dataset and the single‐cell dataset (GSE222300) were retrieved from the Gene Expression Omnibus database. The activation of disease‐related pathways was assessed using Kyoto Encyclopedia of Genes and Genomes, Gene Ontology and differential gene analysis. Disease‐associated genes were identified through differential analysis and weighted gene co‐expression network analysis (WGCNA). The protein–protein interaction network was utilized to pinpoint potential drug targets. Molecular complex detection (MCODE) analysis was employed to uncover relevant genes influenced by butein within key subgroup networks. Machine learning techniques were applied for the screening of potential biomarkers, with receiver operating characteristic curves used to evaluate their clinical significance. Single‐cell analysis was conducted to assess the pharmacological targets of butein in CRC, with validation performed using the external dataset GSE40967.ResultsA total of 232 target genes for butein were identified. Functional enrichment analysis revealed significant enrichment of signaling pathways, including mitogen‐activated protein kinase, JAK‐STAT and NF‐κB, among these genes. Differential analysis, in conjunction with WGCNA, yielded 520 disease‐related genes. Subsequently, a disease‐drug‐gene network consisting of 727 targets was established, and a subnetwork containing 56 crucial genes was extracted. Important pathways such as the FoxO signaling pathway exhibited significant enrichment within these key genes. Machine learning applied to the 56 important genes led to the identification of a potential biomarker, UBE2C. Receiver operating characteristic analysis demonstrated the excellent clinical predictive utility of UBE2C. Single‐cell analysis suggested that butein’s therapeutic effects might be linked to its influence on epithelial and T cells, with UBE2C expression associated with these cell types. Validation using the external dataset GSE40967 further confirmed the exceptional clinical predictive capability of UBE2C.ConclusionThis study combines network pharmacology with single‐cell analysis to unravel the mechanisms underlying butein’s effects in CRC. Notably, UBE2C emerged as a promising biomarker with superior clinical efficacy. These research findings contribute significantly to our understanding of specific molecular mechanisms, potentially shaping future clinical practices.

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“…Butein inhibited the Akt‐Wee1‐CDK1 signaling pathway, reduced survivin Thr34 phosphorylation, and promoted E3 ligase FBXL7‐mediated survivin ubiquitination and degradation. Moreover, Butein alone or combined with cisplatin overcame the chemotherapy resistance of NPC xenografts (Dong et al., 2022).…”

Section: Natural Products That Target Nasopharyngeal Carcinomamentioning

confidence: 99%

The efficacy of natural products for the treatment of nasopharyngeal carcinoma

Ao,

Luo,

Zhang

et al. 2023

Chem Biol Drug Des

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Nasopharyngeal carcinoma (NPC) is a malignant tumor originating in the nasopharyngeal epithelium with a high incidence in southern China and parts of Southeast Asia. The current treatment methods are mainly radiotherapy and chemotherapy. However, they often have side effects and are not suitable for long‐term exposure. Natural products have received more and more attention in cancer prevention and treatment because of their its high efficiency, low toxic side effects, and low toxicity. Natural products can serve as a viable alternative, and this study aimed to review the efficacy and mechanisms of natural products in the treatment of NPC by examining previous literature. Most natural products act by inhibiting cell proliferation, metastasis, inducing cell cycle arrest, and apoptosis. Although further research is needed to verify their effectiveness and safety, natural products can significantly improve the treatment of NPC.

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Butein promotes ubiquitination-mediated survivin degradation inhibits tumor growth and overcomes chemoresistance

Cited by 16 publications

References 38 publications

Ubiquitin-proteasome system-based signature to predict the prognosis and drug sensitivity of hepatocellular carcinoma

Ubiquitin-proteasome system-based signature to predict the prognosis and drug sensitivity of hepatocellular carcinoma

Exploring the mechanism underlying the therapeutic effects of butein in colorectal cancer using network pharmacology and single‐cell RNA sequencing data

The efficacy of natural products for the treatment of nasopharyngeal carcinoma

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