Cancer Letters, Год журнала: 2024, Номер unknown, С. 217419 - 217419
Опубликована: Дек. 1, 2024
Язык: Английский
Journal of Experimental & Clinical Cancer Research, Год журнала: 2024, Номер 43(1)
Опубликована: Сен. 13, 2024
Abstract Background Long-term accumulation of misfolded proteins leads to endoplasmic reticulum (ER) stress in colorectal cancer (CRC). However, the precise pathways controlling decision between survival and apoptosis CRC are unclear. Therefore, this study, we investigated function molecular mechanism glucosidase I (GCS1) regulating ER CRC. Methods A public database was used confirm expression level GCS1 normal tissues. Clinical samples from our center were mRNA protein levels GCS1. Cell proliferation, migration, invasion, assays revealed biological role Immunohistochemical techniques evaluate key subcutaneous implanted tumors nude mice, which provided further evidence for promoting vivo. The results coimmunoprecipitation-mass spectrometry analysis immunofluorescence colocalization interaction GRP78. In addition, action USP10, GRP78, at post- translational investigated. Finally, a tissue microarray examine connection GRP78 intracellular localization these using immunohistochemistry immunofluorescence. Results experimental that substantially expressed CRC, with higher indicating worse prognosis. Thus, can enhance proliferation metastasis while inhibiting cells both vivo vitro. Mechanistically, binds recruits USP10 deubiquitination promote its degradation, decreases stress-mediated apoptosis, increasing cell metastasis. Conclusions summary, stimulates growth migration reduces via USP10-mediated Our findings identify possible therapeutic target
Язык: Английский
Процитировано
4
Journal of Neuro-Oncology, Год журнала: 2025, Номер unknown
Опубликована: Фев. 28, 2025
Язык: Английский
Процитировано
0
Journal of Experimental & Clinical Cancer Research, Год журнала: 2025, Номер 44(1)
Опубликована: Март 11, 2025
Abstract Background Oxaliplatin-based chemotherapy is the first-line treatment for colorectal cancer (CRC). However, oxaliplatin resistance remains a major challenge contributing to failure and poor prognosis. An increased capacity DNA damage repair key mechanism underlying resistance. Although XPA binding protein 2 (XAB2) implicated in various mechanisms, its specific role mediating unclear. Methods XAB2 was identified through analysis of public datasets. Western blot immunohistochemistry were performed evaluate expression, while survival assess clinical significance CRC. Functional experiments then conducted impact on proliferation, repair, RNA sequencing (RNA-seq) Chromatin immunoprecipitation-sequencing (ChIP-seq) used identify target genes. Co-immunoprecipitation (Co-IP) mass spectrometry proteins interacting with XAB2. Dual-luciferase reporter assays, ChIP-qPCR, Co-IP, ubiquitination site spectrometry, ubiquitin assays analyse interactions potential mechanisms involving XAB2, Annexin A2 (ANXA2), ubiquitin-specific protease 10 (USP10). Results found be expressed CRC associated prognosis patients promoted cell proliferation enhanced by promoting repair. Mechanistically, cells treated exhibited USP10 nuclear expression. bound deubiquitinated K48-linked polyubiquitination at K593, thereby stabilising reducing degradation via ubiquitin-proteasome pathway. upregulates ANXA2 expression transcriptional level promoter, mitigating oxaliplatin-induced damage, enhancing Conclusions In summary, this study demonstrates that USP10/XAB2/ANXA2 axis promotes These findings uncover novel suggest therapeutic targets improving efficacy treatment.
Язык: Английский
Процитировано
0
Cell Death and Disease, Год журнала: 2025, Номер 16(1)
Опубликована: Апрель 5, 2025
Abstract Radiotherapy, as a vital means of esophageal cancer treatment, has benefited countless patients, but owing to the occurrence radio-resistance, its therapeutic efficiency been dramatically mitigated. Discovering key biomarkers governing radio-tolerance in and revealing their inherent molecular mechanisms will be great significance for clinical treatment. Here, we have found roundabout guidance receptor 1 (ROBO1) was significantly upregulated cancerous tissues showed enhanced expression with development staging. Cellular experiments demonstrated ROBO1 directly interacted eukaryotic translation initiation factor 3A (eIF3A) accelerated degradation cells after irradiation Mass spectrum analysis further revealed that response irradiation, ROBO1, eIF3A G3BP2 (Ras GTPase-activating protein-binding protein 2) formed hetero-complex triggered lysosomes-mediated degradation. Knocking down abrogated influence on instability. Besides, ROBO1-mediated interrupted P53 process which turn provoked downstream mTOR signaling increased DNA repair associated genes expressions, resulting radio-resistance enhancement cells. In conclusion, our findings novel role modulating P53/mTOR activity provided drug candidate overcoming cancer.
Язык: Английский
Процитировано
0
Cell Death and Disease, Год журнала: 2025, Номер 16(1)
Опубликована: Апрель 10, 2025
Язык: Английский
Процитировано
0
Frontiers in Immunology, Год журнала: 2025, Номер 16
Опубликована: Апрель 15, 2025
Purpose Our study aims to identify the molecular subtypes of genes associated with disulfidptosis in esophageal squamous cell carcinoma(ESCC), develop a prognostic model, and potential therapeutic targets. Methods Based on GSE53625 expression profile data, we identified significant survival differences through consensus cluster analysis. Subsequently, univariate Cox, multivariate LASSO-Cox regression analysis were used establish risk stratification models. The transcriptome data TCGA-ESCC cohort GSE160269 single-cell sequencing dataset integrated verify biological significance further analyze heterogeneity tumor immune microenvironment, explore intercellular communication network, screen targeted drugs, providing theoretical basis for subsequent translational research. Results We two distinct patterns overall survival. Then, constructed signature disulfidptosis, results showed patients high score had worse prognosis. Univariate Cox demonstrated that was an independent factor validated validation set. subgroups differed proportion infiltration related signaling pathways ESCC. exploration immunotherapy confirmed our also certain predictive power immunotherapy. Drug screening suggested AZD8186 JQ1 as therapies high-score patients. Conclusion This provides new ESCC, explores targets, support personalized treatment.
Язык: Английский
Процитировано
0
Clinical and Translational Medicine, Год журнала: 2024, Номер 14(10)
Опубликована: Окт. 1, 2024
Abstract Background Radiotherapy is a primary therapeutic modality for esophageal squamous cell carcinoma (ESCC), but its effectiveness still restricted due to the resistance of cancer cells radiation. Long non‐coding RNAs (lncRNAs) and N 6 ‐methyladenosine (m6A) have been shown play significant roles in tumour radioresistance. However, precise manifestation role m6A‐modified lncRNAs ESCC radioresistance remain unclear. Methods Bioinformatics analysis was conducted identify implicated ESCC. A series functional experiments were performed investigate function LNCAROD Methylated RNA immunoprecipitation, chromatin isolation by purification‐mass spectrometry, co‐immunoprecipitation explore mechanism m6A‐mediated upregulation expression downstream enhancing The efficacy vivo assessed using murine xenograft models. Results Herein, we identified as novel METTL3‐mediated lncRNA that enhanced post‐transcriptionally stabilised YTHDC1. Moreover, confirmed prevented ubiquitin‐proteasome degradation PARP1 protein facilitating PARP1‐NPM1 interaction, thereby contributing homologous recombination‐mediated DNA double‐strand breaks repair radiation cells. Silencing nude mouse model resulted slower growth increased radiosensitivity. Conclusion Our findings enhance understanding lncRNA‐driven machinery underscore significance this context, development potential target patients.
Язык: Английский
Процитировано
3
International Journal of Biological Macromolecules, Год журнала: 2024, Номер 286, С. 138534 - 138534
Опубликована: Дек. 9, 2024
Язык: Английский
Процитировано
2
Cancer Letters, Год журнала: 2024, Номер 594, С. 216994 - 216994
Опубликована: Май 25, 2024
Язык: Английский
Процитировано
1
Cancer Letters, Год журнала: 2024, Номер unknown, С. 217419 - 217419
Опубликована: Дек. 1, 2024
Язык: Английский
Процитировано
0