Hepatology international, 2019-07, Vol.13 (4), p.454-467
2019
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- Autor(en) / Beteiligte
- Titel
- Alteration of splicing factors’ expression during liver disease progression: impact on hepatocellular carcinoma outcome
- Ist Teil von
- Hepatology international, 2019-07, Vol.13 (4), p.454-467
- Ort / Verlag
- New Delhi: Springer India
- Erscheinungsjahr
- 2019
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- Purpose Trans-acting splicing factors (SF) shape the eukaryotic transcriptome by regulating alternative splicing (AS). This process is recurrently modulated in liver cancer suggesting its direct contribution to the course of liver disease. The aim of our study was to investigate the relationship between the regulation of SFs expression and liver damage. Methods The expression profile of 10 liver-specific SF and the AS events of 7 genes associated with liver disorders was assessed by western-blotting in 6 murine models representing different stages of liver damage, from inflammation to hepatocellular carcinoma (HCC). Relevant SFs (PSF, SRSF3, and SRSF6) and target genes ( INSR , SRSF3, and SLK ) modulated in mice were investigated in a cohort of 179 HCC patients. Results Each murine model of liver disease was characterized by a unique SF expression profile. Changes in the SF profile did not affect AS events of the selected genes despite the presence of corresponding splicing sites. In human HCC expression of SFs, including the tumor-suppressor SRSF3, and AS regulation of genes studied were frequently upregulated in tumor versus non-tumor tissues. Risk of tumor recurrence positively correlated with AS isoform of the INSR gene. In contrast, increased levels of SFs expression correlated with an extended overall survival of patients. Conclusions Dysregulation of SF expression is an early event occurring during liver injury and not just at the stage of HCC. Besides impacting on AS regulation, overexpression of SF may contribute to preserving hepatocyte homeostasis during liver pathogenesis.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 1936-0533eISSN: 1936-0541DOI: 10.1007/s12072-019-09950-7Titel-ID: cdi_hal_primary_oai_HAL_hal_03994466v1
- Format
- –
- Schlagworte
- Alternative splicing, Alternative Splicing - genetics, Animal models, Animals, Carcinoma, Hepatocellular - genetics, Carcinoma, Hepatocellular - metabolism, Carcinoma, Hepatocellular - mortality, Colorectal Surgery, Disease Models, Animal, Disease Progression, Female, Gene expression, Gene regulation, Genes, Hepatocellular carcinoma, Hepatology, Homeostasis, Humans, Immunology, Life Sciences, Liver, Liver cancer, Liver diseases, Liver Diseases - genetics, Liver Diseases - metabolism, Liver Diseases - mortality, Liver Neoplasms - genetics, Liver Neoplasms - metabolism, Liver Neoplasms - mortality, Male, Medicine, Medicine & Public Health, Mice, Inbred C57BL, Middle Aged, Neoplasm Recurrence, Local, Original Article, Pathogenesis, RNA Splicing Factors - metabolism, Splicing factors, Surgery, Tumors