Proteomic Profiling Identifies Co-Regulated Expression of Splicing Factors as a Characteristic Feature of Intravenous Leiomyomatosis
Intravenous leiomyomatosis (IVLM) is a rare benign smooth muscle tumour that is characterised by intravenous growth in the uterine and pelvic veins. Previous DNA copy number and transcriptomic studies have shown that IVLM harbors unique genomic and transcriptomic alterations when compared to uterine...
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-06-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/14/12/2907 |
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| author | Lukas Krasny Chris P. Wilding Emma Perkins Amani Arthur Nafia Guljar Andrew D. Jenks Cyril Fisher Ian Judson Khin Thway Robin L. Jones Paul H. Huang |
| author_facet | Lukas Krasny Chris P. Wilding Emma Perkins Amani Arthur Nafia Guljar Andrew D. Jenks Cyril Fisher Ian Judson Khin Thway Robin L. Jones Paul H. Huang |
| author_sort | Lukas Krasny |
| collection | DOAJ |
| description | Intravenous leiomyomatosis (IVLM) is a rare benign smooth muscle tumour that is characterised by intravenous growth in the uterine and pelvic veins. Previous DNA copy number and transcriptomic studies have shown that IVLM harbors unique genomic and transcriptomic alterations when compared to uterine leiomyoma (uLM), which may account for their distinct clinical behaviour. Here we undertake the first comparative proteomic analysis of IVLM and other smooth muscle tumours (comprising uLM, soft tissue leiomyoma and benign metastasizing leiomyoma) utilising data-independent acquisition mass spectrometry. We show that, at the protein level, IVLM is defined by the unique co-regulated expression of splicing factors. In particular, IVLM is enriched in two clusters composed of co-regulated proteins from the hnRNP, LSm, SR and Sm classes of the spliceosome complex. One of these clusters (Cluster 3) is associated with key biological processes including nascent protein translocation and cell signalling by small GTPases. Taken together, our study provides evidence of co-regulated expression of splicing factors in IVLM compared to other smooth muscle tumours, which suggests a possible role for alternative splicing in the pathogenesis of IVLM. |
| first_indexed | 2024-03-10T00:13:23Z |
| format | Article |
| id | doaj.art-c02fac6476b3411081c629d83883a382 |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-10T00:13:23Z |
| publishDate | 2022-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-c02fac6476b3411081c629d83883a3822023-11-23T15:56:13ZengMDPI AGCancers2072-66942022-06-011412290710.3390/cancers14122907Proteomic Profiling Identifies Co-Regulated Expression of Splicing Factors as a Characteristic Feature of Intravenous LeiomyomatosisLukas Krasny0Chris P. Wilding1Emma Perkins2Amani Arthur3Nafia Guljar4Andrew D. Jenks5Cyril Fisher6Ian Judson7Khin Thway8Robin L. Jones9Paul H. Huang10Division of Molecular Pathology, The Institute of Cancer Research, London SM2 5NG, UKDivision of Molecular Pathology, The Institute of Cancer Research, London SM2 5NG, UKDivision of Molecular Pathology, The Institute of Cancer Research, London SM2 5NG, UKDivision of Molecular Pathology, The Institute of Cancer Research, London SM2 5NG, UKDivision of Molecular Pathology, The Institute of Cancer Research, London SM2 5NG, UKDivision of Molecular Pathology, The Institute of Cancer Research, London SM2 5NG, UKUniversity Hospitals Birmingham NHS Foundation Trust, Birmingham B15 2GW, UKThe Royal Marsden NHS Foundation Trust, London SW3 6JJ, UKDivision of Molecular Pathology, The Institute of Cancer Research, London SM2 5NG, UKThe Royal Marsden NHS Foundation Trust, London SW3 6JJ, UKDivision of Molecular Pathology, The Institute of Cancer Research, London SM2 5NG, UKIntravenous leiomyomatosis (IVLM) is a rare benign smooth muscle tumour that is characterised by intravenous growth in the uterine and pelvic veins. Previous DNA copy number and transcriptomic studies have shown that IVLM harbors unique genomic and transcriptomic alterations when compared to uterine leiomyoma (uLM), which may account for their distinct clinical behaviour. Here we undertake the first comparative proteomic analysis of IVLM and other smooth muscle tumours (comprising uLM, soft tissue leiomyoma and benign metastasizing leiomyoma) utilising data-independent acquisition mass spectrometry. We show that, at the protein level, IVLM is defined by the unique co-regulated expression of splicing factors. In particular, IVLM is enriched in two clusters composed of co-regulated proteins from the hnRNP, LSm, SR and Sm classes of the spliceosome complex. One of these clusters (Cluster 3) is associated with key biological processes including nascent protein translocation and cell signalling by small GTPases. Taken together, our study provides evidence of co-regulated expression of splicing factors in IVLM compared to other smooth muscle tumours, which suggests a possible role for alternative splicing in the pathogenesis of IVLM.https://www.mdpi.com/2072-6694/14/12/2907proteomicsspliceosomesplicing factorsleiomyomaintravenous leiomyomatosis |
| spellingShingle | Lukas Krasny Chris P. Wilding Emma Perkins Amani Arthur Nafia Guljar Andrew D. Jenks Cyril Fisher Ian Judson Khin Thway Robin L. Jones Paul H. Huang Proteomic Profiling Identifies Co-Regulated Expression of Splicing Factors as a Characteristic Feature of Intravenous Leiomyomatosis Cancers proteomics spliceosome splicing factors leiomyoma intravenous leiomyomatosis |
| title | Proteomic Profiling Identifies Co-Regulated Expression of Splicing Factors as a Characteristic Feature of Intravenous Leiomyomatosis |
| title_full | Proteomic Profiling Identifies Co-Regulated Expression of Splicing Factors as a Characteristic Feature of Intravenous Leiomyomatosis |
| title_fullStr | Proteomic Profiling Identifies Co-Regulated Expression of Splicing Factors as a Characteristic Feature of Intravenous Leiomyomatosis |
| title_full_unstemmed | Proteomic Profiling Identifies Co-Regulated Expression of Splicing Factors as a Characteristic Feature of Intravenous Leiomyomatosis |
| title_short | Proteomic Profiling Identifies Co-Regulated Expression of Splicing Factors as a Characteristic Feature of Intravenous Leiomyomatosis |
| title_sort | proteomic profiling identifies co regulated expression of splicing factors as a characteristic feature of intravenous leiomyomatosis |
| topic | proteomics spliceosome splicing factors leiomyoma intravenous leiomyomatosis |
| url | https://www.mdpi.com/2072-6694/14/12/2907 |
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