The landscape of alternative splicing in cervical squamous cell carcinoma

• Main Authors: Guo P, Wang D, Wu J, Yang J, Ren T, Zhu B, Xiang Y
• Format: Article
• Language: English
• Published: Dove Medical Press 2014-12-01
• Series: OncoTargets and Therapy
• Online Access: http://www.dovepress.com/the-landscape-of-alternative-splicing-in-cervical-squamous-cell-carcin-peer-reviewed-article-OTT

Peng Guo,1 Dan Wang,1 Jun Wu,2 Junjun Yang,1 Tong Ren,1 Baoli Zhu,2 Yang Xiang1 1Department of Obstetrics and Gynecology, Peking Union Medical College Hospital, Beijing, People’s Republic of China; 2CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, People’s Republic of China Background: Alternative splicing (AS) is a key regulatory mechanism in protein synthesis and proteome diversity. In this study, we identified alternative splicing events in four pairs of cervical squamous cell carcinoma (CSCC) and adjacent nontumor tissues using RNA sequencing. Methods: The transcripts of the four paired samples were thoroughly analyzed by RNA sequencing. SpliceMap software was used to detect the splicing junctions. Kyoto Encyclopedia of Genes and Genomes pathway analysis was conducted to detect the alternative spliced genes-related signal pathways. The alternative spliced genes were validated by reverse transcription-polymerase chain reaction (RT-PCR). Results: There were 35 common alternative spliced genes in the four CSCC samples; they were novel and CSCC specific. Sixteen pathways were significantly enriched (P<0.05). One novel 5'AS site in the KLHDC7B gene, encoding kelch domain-containing 7B, and an exon-skipping site in the SYCP2 gene, encoding synaptonemal complex 2, were validated by RT-PCR. The KLHDC7B gene with 5'AS was found in 67.5% (27/40) of CSCC samples and was significantly related with cellular differentiation and tumor size. The exon-skipping site of the SYCP2 gene was found in 35.0% (14/40) of CSCC samples and was significantly related with depth of cervical invasion. Conclusion: The KLHDC7B and the SYCP2 genes with alternative spliced events might be involved in the development and progression of CSCC and could be used as biomarkers in the diagnosis and prognosis of CSCC. Keywords: cervical squamous carcinomas, alternative splicing events, RNA sequencing