An in-silico pan-cancer bulk and single-cell profiling of transcription factors in protein autoubiquitination
Abstract The protein autoubiquitination has emerged as a significant focus in pan-cancer genetic research due to its potential impact on cancer progression and treatment. Protein autoubiquitination regulates the stability, activity, and localization of involved proteins, playing a crucial role in va...
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| Format: | Article |
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Springer
2025-07-01
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| Series: | Discover Oncology |
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| Online Access: | https://doi.org/10.1007/s12672-025-03067-0 |
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| author | Angela Dong Ayana Rasteh Panpan Wang Hengrui Liu |
| author_facet | Angela Dong Ayana Rasteh Panpan Wang Hengrui Liu |
| author_sort | Angela Dong |
| collection | DOAJ |
| description | Abstract The protein autoubiquitination has emerged as a significant focus in pan-cancer genetic research due to its potential impact on cancer progression and treatment. Protein autoubiquitination regulates the stability, activity, and localization of involved proteins, playing a crucial role in various cellular processes, including signal transduction, protein quality control, and immune response regulation. This mechanism is vital for maintaining cellular homeostasis and adapting to environmental changes or stress, such as tumor growth. Insights into these processes could lead to novel therapeutic strategies targeting the ubiquitin-proteasome system. This study examines the clinical relevance of transcription factors associated with protein autoubiquitination genes, including CNOT4, MTA1, NFX1, RNF10, RNF112, RNF115, RNF13, RNF141, RNF4, RNF8, TAF1, TRIM13, and UHRF1. Using multi-omics profiling data and Gene Set Cancer Analysis (GSCA) with normalized SEM mRNA expression, the study evaluates differential expression, gene mutations, and drug correlations. The analysis revealed that the single nucleotide variant (SNV) heatmap indicated high mutation frequencies for many of these genes across various cancer types. Gene expression analysis showed limited overall significance, but TAF1 was notably upregulated in uterine corpus endometrial carcinoma (UCEC), while RNF115 and RNF141 were downregulated in the same cancer type. Copy number variation (CNV) profiles exhibited diverse patterns across cancer types, and methylation profiles suggested differences in methylation levels between tumor and normal tissues. Additionally, single-cell transcriptomic analysis uncovered cancer-type-specific functional states. This research highlights the importance of understanding autoubiquitination genes in cancer biology, which may aid in developing effective diagnostic and prognostic strategies. However, the analysis is limited to experimental evidence. However, these findings derive solely from publicly available datasets and lack experimental validation, which may introduce bias. Single-cell analyses cover only a few tumor types, drug-gene relationships remain correlative, and the absence of longitudinal clinical data prevents evaluation of true prognostic value. |
| format | Article |
| id | doaj-art-3c6a1637e7c645e4a590db2d26b2a555 |
| institution | Kabale University |
| issn | 2730-6011 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Springer |
| record_format | Article |
| series | Discover Oncology |
| spelling | doaj-art-3c6a1637e7c645e4a590db2d26b2a5552025-08-20T04:01:36ZengSpringerDiscover Oncology2730-60112025-07-0116111310.1007/s12672-025-03067-0An in-silico pan-cancer bulk and single-cell profiling of transcription factors in protein autoubiquitinationAngela Dong0Ayana Rasteh1Panpan Wang2Hengrui Liu3Havergal CollegeArchbishop Mitty High SchoolGuangdong Provincial Key Laboratory of Traditional Chinese Medicine InformatizationGuangdong Provincial Key Laboratory of Traditional Chinese Medicine InformatizationAbstract The protein autoubiquitination has emerged as a significant focus in pan-cancer genetic research due to its potential impact on cancer progression and treatment. Protein autoubiquitination regulates the stability, activity, and localization of involved proteins, playing a crucial role in various cellular processes, including signal transduction, protein quality control, and immune response regulation. This mechanism is vital for maintaining cellular homeostasis and adapting to environmental changes or stress, such as tumor growth. Insights into these processes could lead to novel therapeutic strategies targeting the ubiquitin-proteasome system. This study examines the clinical relevance of transcription factors associated with protein autoubiquitination genes, including CNOT4, MTA1, NFX1, RNF10, RNF112, RNF115, RNF13, RNF141, RNF4, RNF8, TAF1, TRIM13, and UHRF1. Using multi-omics profiling data and Gene Set Cancer Analysis (GSCA) with normalized SEM mRNA expression, the study evaluates differential expression, gene mutations, and drug correlations. The analysis revealed that the single nucleotide variant (SNV) heatmap indicated high mutation frequencies for many of these genes across various cancer types. Gene expression analysis showed limited overall significance, but TAF1 was notably upregulated in uterine corpus endometrial carcinoma (UCEC), while RNF115 and RNF141 were downregulated in the same cancer type. Copy number variation (CNV) profiles exhibited diverse patterns across cancer types, and methylation profiles suggested differences in methylation levels between tumor and normal tissues. Additionally, single-cell transcriptomic analysis uncovered cancer-type-specific functional states. This research highlights the importance of understanding autoubiquitination genes in cancer biology, which may aid in developing effective diagnostic and prognostic strategies. However, the analysis is limited to experimental evidence. However, these findings derive solely from publicly available datasets and lack experimental validation, which may introduce bias. Single-cell analyses cover only a few tumor types, drug-gene relationships remain correlative, and the absence of longitudinal clinical data prevents evaluation of true prognostic value.https://doi.org/10.1007/s12672-025-03067-0UbiquitinationProteinPan-cancersMutationPrognosis |
| spellingShingle | Angela Dong Ayana Rasteh Panpan Wang Hengrui Liu An in-silico pan-cancer bulk and single-cell profiling of transcription factors in protein autoubiquitination Discover Oncology Ubiquitination Protein Pan-cancers Mutation Prognosis |
| title | An in-silico pan-cancer bulk and single-cell profiling of transcription factors in protein autoubiquitination |
| title_full | An in-silico pan-cancer bulk and single-cell profiling of transcription factors in protein autoubiquitination |
| title_fullStr | An in-silico pan-cancer bulk and single-cell profiling of transcription factors in protein autoubiquitination |
| title_full_unstemmed | An in-silico pan-cancer bulk and single-cell profiling of transcription factors in protein autoubiquitination |
| title_short | An in-silico pan-cancer bulk and single-cell profiling of transcription factors in protein autoubiquitination |
| title_sort | in silico pan cancer bulk and single cell profiling of transcription factors in protein autoubiquitination |
| topic | Ubiquitination Protein Pan-cancers Mutation Prognosis |
| url | https://doi.org/10.1007/s12672-025-03067-0 |
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