TF–RBP–AS Triplet Analysis Reveals the Mechanisms of Aberrant Alternative Splicing Events in Kidney Cancer: Implications for Their Possible Clinical Use as Prognostic and Therapeutic Biomarkers
Aberrant alternative splicing (AS) is increasingly linked to cancer; however, how AS contributes to cancer development still remains largely unknown. AS events (ASEs) are largely regulated by RNA-binding proteins (RBPs) whose ability can be modulated by a variety of genetic and epigenetic mechanisms...
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| Format: | Article |
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MDPI AG
2021-08-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/22/16/8789 |
| _version_ | 1797523608460853248 |
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| author | Meng He Fuyan Hu |
| author_facet | Meng He Fuyan Hu |
| author_sort | Meng He |
| collection | DOAJ |
| description | Aberrant alternative splicing (AS) is increasingly linked to cancer; however, how AS contributes to cancer development still remains largely unknown. AS events (ASEs) are largely regulated by RNA-binding proteins (RBPs) whose ability can be modulated by a variety of genetic and epigenetic mechanisms. In this study, we used a computational framework to investigate the roles of transcription factors (TFs) on regulating RBP-AS interactions. A total of 6519 TF–RBP–AS triplets were identified, including 290 TFs, 175 RBPs, and 16 ASEs from TCGA–KIRC RNA sequencing data. TF function categories were defined according to correlation changes between RBP expression and their targeted ASEs. The results suggested that most TFs affected multiple targets, and six different classes of TF-mediated transcriptional dysregulations were identified. Then, regulatory networks were constructed for TF–RBP–AS triplets. Further pathway-enrichment analysis showed that these TFs and RBPs involved in triplets were enriched in a variety of pathways that were associated with cancer development and progression. Survival analysis showed that some triplets were highly associated with survival rates. These findings demonstrated that the integration of TFs into alternative splicing regulatory networks can help us in understanding the roles of alternative splicing in cancer. |
| first_indexed | 2024-03-10T08:45:23Z |
| format | Article |
| id | doaj.art-fc72241a4b0044168b15751f194221cb |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T08:45:23Z |
| publishDate | 2021-08-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-fc72241a4b0044168b15751f194221cb2023-11-22T08:00:38ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-08-012216878910.3390/ijms22168789TF–RBP–AS Triplet Analysis Reveals the Mechanisms of Aberrant Alternative Splicing Events in Kidney Cancer: Implications for Their Possible Clinical Use as Prognostic and Therapeutic BiomarkersMeng He0Fuyan Hu1Department of Statistics, School of Science, Wuhan University of Technology, 122 Luoshi Road, Wuhan 430070, ChinaDepartment of Statistics, School of Science, Wuhan University of Technology, 122 Luoshi Road, Wuhan 430070, ChinaAberrant alternative splicing (AS) is increasingly linked to cancer; however, how AS contributes to cancer development still remains largely unknown. AS events (ASEs) are largely regulated by RNA-binding proteins (RBPs) whose ability can be modulated by a variety of genetic and epigenetic mechanisms. In this study, we used a computational framework to investigate the roles of transcription factors (TFs) on regulating RBP-AS interactions. A total of 6519 TF–RBP–AS triplets were identified, including 290 TFs, 175 RBPs, and 16 ASEs from TCGA–KIRC RNA sequencing data. TF function categories were defined according to correlation changes between RBP expression and their targeted ASEs. The results suggested that most TFs affected multiple targets, and six different classes of TF-mediated transcriptional dysregulations were identified. Then, regulatory networks were constructed for TF–RBP–AS triplets. Further pathway-enrichment analysis showed that these TFs and RBPs involved in triplets were enriched in a variety of pathways that were associated with cancer development and progression. Survival analysis showed that some triplets were highly associated with survival rates. These findings demonstrated that the integration of TFs into alternative splicing regulatory networks can help us in understanding the roles of alternative splicing in cancer.https://www.mdpi.com/1422-0067/22/16/8789alternative splicingRNA-binding proteintranscription factorTF–RBP–AS tripletsregulation mechanism |
| spellingShingle | Meng He Fuyan Hu TF–RBP–AS Triplet Analysis Reveals the Mechanisms of Aberrant Alternative Splicing Events in Kidney Cancer: Implications for Their Possible Clinical Use as Prognostic and Therapeutic Biomarkers International Journal of Molecular Sciences alternative splicing RNA-binding protein transcription factor TF–RBP–AS triplets regulation mechanism |
| title | TF–RBP–AS Triplet Analysis Reveals the Mechanisms of Aberrant Alternative Splicing Events in Kidney Cancer: Implications for Their Possible Clinical Use as Prognostic and Therapeutic Biomarkers |
| title_full | TF–RBP–AS Triplet Analysis Reveals the Mechanisms of Aberrant Alternative Splicing Events in Kidney Cancer: Implications for Their Possible Clinical Use as Prognostic and Therapeutic Biomarkers |
| title_fullStr | TF–RBP–AS Triplet Analysis Reveals the Mechanisms of Aberrant Alternative Splicing Events in Kidney Cancer: Implications for Their Possible Clinical Use as Prognostic and Therapeutic Biomarkers |
| title_full_unstemmed | TF–RBP–AS Triplet Analysis Reveals the Mechanisms of Aberrant Alternative Splicing Events in Kidney Cancer: Implications for Their Possible Clinical Use as Prognostic and Therapeutic Biomarkers |
| title_short | TF–RBP–AS Triplet Analysis Reveals the Mechanisms of Aberrant Alternative Splicing Events in Kidney Cancer: Implications for Their Possible Clinical Use as Prognostic and Therapeutic Biomarkers |
| title_sort | tf rbp as triplet analysis reveals the mechanisms of aberrant alternative splicing events in kidney cancer implications for their possible clinical use as prognostic and therapeutic biomarkers |
| topic | alternative splicing RNA-binding protein transcription factor TF–RBP–AS triplets regulation mechanism |
| url | https://www.mdpi.com/1422-0067/22/16/8789 |
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