title: Global profiling of alternative RNA splicing events provides insights into molecular differences between various types of hepatocellular carcinoma.
abstract: 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.
  
  
  
  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.
  
  
  
  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.
authors: 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.
authors: Marie-Pier
authors: MP
authors: Tremblay
authors: 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.
authors: Victoria E S
authors: VE
authors: Armero
authors: 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.
authors: Andréa
authors: A
authors: Allaire
authors: 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.
authors: Simon
authors: S
authors: Boudreault
authors: 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.
authors: Camille
authors: C
authors: Martenon-Brodeur
authors: Plateforme RNomique, Université de Sherbrooke, Sherbrooke, QC, J1E 4K8, Canada.
authors: Mathieu
authors: M
authors: Durand
authors: Plateforme RNomique, Université de Sherbrooke, Sherbrooke, QC, J1E 4K8, Canada.
authors: Elvy
authors: E
authors: Lapointe
authors: Plateforme RNomique, Université de Sherbrooke, Sherbrooke, QC, J1E 4K8, Canada.
authors: Philippe
authors: P
authors: Thibault
authors: 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.
authors: Maude
authors: M
authors: Tremblay-Létourneau
authors: 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.
authors: Jean-Pierre
authors: JP
authors: Perreault
authors: 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.
authors: Michelle S
authors: MS
authors: Scott
authors: 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.
authors: Martin
authors: 0000-0001-7822-0933
authors: M
authors: Bisaillon
mesh_terms: D017398:Alternative Splicing; D006528:Carcinoma, Hepatocellular / Q000175:diagnosis / Q000235:genetics* / Q000821:virology; D016000:Cluster Analysis; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006509:Hepatitis B / Q000150:complications; D006526:Hepatitis C / Q000150:complications; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D008113:Liver Neoplasms / Q000175:diagnosis / Q000235:genetics* / Q000821:virology; D000072260:RNA Splicing Factors / Q000235:genetics; D012333:RNA, Messenger; D015203:Reproducibility of Results; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism; D059467:Transcriptome; D054334:Viral Regulatory and Accessory Proteins
chemical_list: D000072260:RNA Splicing Factors; D012333:RNA, Messenger; D015534:Trans-Activators; D054334:Viral Regulatory and Accessory Proteins; C057628:hepatitis B virus X protein
keywords: Gene dysregulation; Hepatitis B virus; Hepatitis C virus; Liver cancer; RNA splicing