The landscape of alternative splicing in cervical squamous cell carcinoma.
The landscape of alternative splicing in cervical squamous cell carcinoma.
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DOI：
10.2147/ott.s72832
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发表时间：
2015
影响因子：
4
通讯作者：
Xiang Y
中科院分区：
文献类型：
--
作者：
Guo P;Wang D;Wu J;Yang J;Ren T;Zhu B;Xiang Y
选择性剪接(AS)是蛋白质合成和蛋白质组多样性的关键调控机制。在这项研究中，我们通过RNA测序确定了四对宫颈鳞状细胞癌(CSCC)及其邻近非肿瘤组织中的选择性剪接事件。对四个配对样本的转录本进行了RNA测序。用SpliceMap软件检测剪接连接。通过《京都百科全书》的基因和基因组途径分析，寻找与基因选择性剪接相关的信号通路。用逆转录-聚合酶链式反应(RT-PCR)对选择性剪接基因进行验证。在4个CSCC样本中有35个常见的选择性剪接基因，它们是新的和CSCC特有的。16条通路显著丰富(P<；0.05)。通过RT-PCR验证了KLHDC7B基因中编码kelch结构域7B的一个新的5‘AS位点和编码突触膜复合体2的SYCP2基因中的一个外显子跳跃位点。67.5%(27/40)的CSCC组织中存在KLHDC7B基因5‘端缺失，且KLHDC7B基因与细胞分化程度和肿瘤大小密切相关。SYCP2基因外显子跳跃位点在35.0%(14/40)的宫颈鳞癌组织中存在，且与宫颈浸润深度显著相关。具有选择性剪接事件的KLHDC7B和SYCP2基因可能参与了宫颈鳞癌的发生发展，可作为宫颈鳞癌诊断和预后的生物标志物。
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. 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). 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. 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.