Huang Yi, Zheng Jiaying, Chen Dunyan, Li Feng, Wu Wenbing, Huang Xiaoli, Wu Yanan, Deng Yangyang, Qiu Funan
Provincial Clinical College, Fujian Medical University, Fuzhou 350001, Fujian, China.
Department of Clinical Laboratory, Fujian Provincial Hospital, Fuzhou 350001, Fujian, China.
Oncotarget. 2017 Jun 20;8(25):40693-40704. doi: 10.18632/oncotarget.17244.
We performed transcriptome sequencing for hepatocellular carcinoma (HCC) and adjacent non-tumorous tissues to investigate the molecular basis of HCC. Nine HCC patients were recruited and differentially expressed genes (DEGs) were identified. Candidate fusion transcripts were also identified. A total of 1943 DEGs were detected, including 690 up-regulated and 1253 down-regulated genes, and enriched in ten pathways including cell cycle, DNA replication, p53, complement and coagulation cascades, etc. Seven candidate fusion genes were detected and CRYL1-IFT88 was successfully validated in the discovery sequencing sample and another 5 tumor samples with the recurrent rate of about 9.52% (6/63). The full length of CRYL1-IFT88 was obtained by 3' and 5' RACE. The function of the fusion transcript is closed to CRYL1 because it contained most of domain of CRYL1. According to the bioinformatics analysis, IFT88, reported as a tumor suppressor, might be seriously depressed in the tumor cell with this fusion because the transcript structure of IFT88 was totally changed. The function depression of IFT88 caused by gene fusion CRYL1-IFT88 might be associated with tumorigenesis or development of HCC.
我们对肝细胞癌（HCC）及其癌旁非肿瘤组织进行了转录组测序，以探究HCC的分子基础。招募了9例HCC患者，并鉴定出差异表达基因（DEG）。还鉴定出了候选融合转录本。共检测到1943个DEG，其中包括690个上调基因和1253个下调基因，并富集于细胞周期、DNA复制、p53、补体和凝血级联反应等十条通路中。检测到7个候选融合基因，CRYL1-IFT88在发现测序样本及另外5个肿瘤样本中成功得到验证，复发率约为9.52%（6/63）。通过3'和5' RACE获得了CRYL1-IFT88的全长。该融合转录本的功能与CRYL1接近，因为它包含了CRYL1的大部分结构域。根据生物信息学分析，据报道作为肿瘤抑制因子的IFT88，在带有这种融合的肿瘤细胞中可能会受到严重抑制，因为IFT88的转录本结构完全改变了。由基因融合CRYL1-IFT88导致的IFT88功能抑制可能与HCC的发生或发展有关。
