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BMC Genomics. 2016 Aug 26;17:683. doi: 10.1186/s12864-016-3029-z.

Global profiling of alternative RNA splicing events provides insights into molecular differences between various types of hepatocellular carcinoma.

Author information

1
Département de biochimie, Pavillon de recherche appliquée sur le cancer, Faculté de médecine et des sciences de la santé, Université de Sherbrooke, 3201 Jean-Mignault, Sherbrooke, QC, J1E 4K8, Canada.
2
Plateforme RNomique, Université de Sherbrooke, Sherbrooke, QC, J1E 4K8, Canada.
3
Département de biochimie, Pavillon de recherche appliquée sur le cancer, Faculté de médecine et des sciences de la santé, Université de Sherbrooke, 3201 Jean-Mignault, Sherbrooke, QC, J1E 4K8, Canada. Martin.Bisaillon@USherbrooke.ca.

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.

KEYWORDS:

Gene dysregulation; Hepatitis B virus; Hepatitis C virus; Liver cancer; RNA splicing

PMID:
27565572
PMCID:
PMC5002109
DOI:
10.1186/s12864-016-3029-z
[Indexed for MEDLINE]
Free PMC Article

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