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

BMC Genomics

Research Article

Maude Tremblay-Létourneau¹  Michelle S. Scott¹  Camille Martenon-Brodeur¹  Jean-Pierre Perreault¹  Marie-Pier Tremblay¹  Victoria E. S. Armero¹  Martin Bisaillon¹  Andréa Allaire¹  Simon Boudreault¹  Elvy Lapointe²  Mathieu Durand²  Philippe Thibault² 

[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, J1E 4K8, Sherbrooke, QC, Canada;Plateforme RNomique, Université de Sherbrooke, J1E 4K8, Sherbrooke, QC, Canada;

关键词: Liver cancer;    Hepatitis B virus;    Hepatitis C virus;    RNA splicing;    Gene dysregulation;   

DOI  :  10.1186/s12864-016-3029-z

 received in 2016-05-31, accepted in 2016-08-20,  发布年份 2016

来源: Springer

【 摘 要 】

BackgroundDysregulations 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.ResultsOur 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.ConclusionsThis 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.

【 授权许可】

CC BY   
© The Author(s). 2016