Sun Mingzhong, Ju Huixiang, Zhou Zhongwei, Zhu Rong
Department of Clinical Laboratory, Affiliated Yancheng Hospital, School of Medicine, Southeast University, Yancheng, Jiangsu 224001, P.R. China.
Mol Med Rep. 2014 May;9(5):1597-605. doi: 10.3892/mmr.2014.2003. Epub 2014 Mar 4.
Regulatory regions within the 3' untranslated region (UTR) influence polyadenylation (polyA), translation efficiency, localization and stability of mRNA. Alternative polyA (APA) has been considered to have a key role in gene regulation since 2008. Esophageal carcinoma is the eighth most common type of cancer worldwide. The association between polyA and disease highlights the requirement for comprehensive characterization of genome-wide polyA profiles. In the present study, global polyA profiles were established using the sequencing APA sites (SAPAS) method in order to elucidate the interrelation between 3' UTR length and the development of esophageal cancer. PolyA profiles were analyzed in squamous cell carcinoma, with ~903 genes identified to have shortened 3' UTRs and 917 genes identified to use distal polyA sites. The genes with shortened 3' UTRs were primarily associated with adherens junctions and the cell cycle. Four differentially expressed genes were also found, among which three genes were observed to be upregulated in cancerous tissue and involved in the positive regulation of cell motion, migration and locomotion. One gene was found to be downregulated in cancerous tissue, and associated with oxidative phosphorylation. These findings suggest that esophagitis may have a key role in the development of esophageal carcinoma. Furthermore, the genes with tandem 3' UTRs and differential expression identified in the present study may have the potential to be used as biomarkers for the diagnosis and prognosis of esophageal cancer.
3'非翻译区（UTR）内的调控区域会影响多聚腺苷酸化（polyA）、翻译效率、mRNA的定位和稳定性。自2008年以来，可变多聚腺苷酸化（APA）就被认为在基因调控中起关键作用。食管癌是全球第八大常见癌症类型。多聚腺苷酸化与疾病之间的关联凸显了全面表征全基因组多聚腺苷酸化图谱的必要性。在本研究中，为了阐明3'UTR长度与食管癌发生发展之间的相互关系，采用测序APA位点（SAPAS）方法建立了全基因组多聚腺苷酸化图谱。对鳞状细胞癌中的多聚腺苷酸化图谱进行了分析，发现约903个基因的3'UTR缩短，917个基因使用远端多聚腺苷酸化位点。3'UTR缩短的基因主要与黏着连接和细胞周期相关。还发现了四个差异表达基因，其中三个基因在癌组织中上调，参与细胞运动、迁移和移动的正调控。发现一个基因在癌组织中下调，并与氧化磷酸化相关。这些发现表明食管炎可能在食管癌的发生发展中起关键作用。此外，本研究中鉴定出的具有串联3'UTR和差异表达的基因可能有潜力用作食管癌诊断和预后的生物标志物。
