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Global profiling of alternative RNA splicing events provides insights into molecular differences between various types of hepatocellular carcinoma
- Source :
- BMC Genomics
- Publication Year :
- 2016
-
Abstract
- Background Dysregulations in alternative splicing (AS) patterns have been associated with many human diseases including cancer. In the present study, alterations to the global RNA splicing landscape of cellular genes were investigated in a large-scale screen from 377 liver tissue samples using high-throughput RNA sequencing data. Results Our study identifies modifications in the AS patterns of transcripts encoded by more than 2500 genes such as tumor suppressor genes, transcription factors, and kinases. These findings provide insights into the molecular differences between various types of hepatocellular carcinoma (HCC). Our analysis allowed the identification of 761 unique transcripts for which AS is misregulated in HBV-associated HCC, while 68 are unique to HCV-associated HCC, 54 to HBV&HCV-associated HCC, and 299 to virus-free HCC. Moreover, we demonstrate that the expression pattern of the RNA splicing factor hnRNPC in HCC tissues significantly correlates with patient survival. We also show that the expression of the HBx protein from HBV leads to modifications in the AS profiles of cellular genes. Finally, using RNA interference and a reverse transcription-PCR screening platform, we examined the implications of cellular proteins involved in the splicing of transcripts involved in apoptosis and demonstrate the potential contribution of these proteins in AS control. Conclusions This study provides the first comprehensive portrait of global changes in the RNA splicing signatures that occur in hepatocellular carcinoma. Moreover, these data allowed us to identify unique signatures of genes for which AS is misregulated in the different types of HCC. Electronic supplementary material The online version of this article (doi:10.1186/s12864-016-3029-z) contains supplementary material, which is available to authorized users.
- Subjects :
- 0301 basic medicine
RNA Splicing Factors
Hepatitis B virus
Carcinoma, Hepatocellular
RNA splicing
Computational biology
Biology
Transcriptome
03 medical and health sciences
RNA interference
Genetics
Cluster Analysis
Humans
Viral Regulatory and Accessory Proteins
RNA, Messenger
Gene
Hepatitis C virus
Gene Expression Profiling
Alternative splicing
Liver Neoplasms
RNA
High-Throughput Nucleotide Sequencing
Reproducibility of Results
Gene dysregulation
Hepatitis B
Hepatitis C
digestive system diseases
Gene expression profiling
Gene Expression Regulation, Neoplastic
Alternative Splicing
030104 developmental biology
Trans-Activators
Liver cancer
Biotechnology
Research Article
Subjects
Details
- ISSN :
- 14712164
- Volume :
- 17
- Database :
- OpenAIRE
- Journal :
- BMC genomics
- Accession number :
- edsair.doi.dedup.....a750c64cf0ee7a438c9476bac4c847e5