Immature Colon Carcinoma Transcript-1 (ICT1) Expression Correlates with Unfavorable Prognosis and Survival in Patients with Colorectal Cancer
Immature Colon Carcinoma Transcript-1 (ICT1) Expression Correlates with Unfavorable Prognosis and Survival in Patients with Colorectal Cancer
复制标题
未成熟结肠癌转录物-1 (ICT1) 表达与结直肠癌患者的不良预后和生存相关
DOI：
10.1245/s10434-016-5305-1
复制
发表时间：
2016-11-01
影响因子：
3.7
通讯作者：
Qin, Xinyu
中科院分区：
文献类型：
--
作者：
Lao, Xinyuan;Feng, Qingyang;Qin, Xinyu
结直肠癌（CRC）是全球癌症死亡的第三大原因。据报道，未成熟结肠癌转录-1 （ICT1）与肺癌相关；然而，ICT1在结直肠癌中是否是一个功能基因，以及ICT1介导结直肠肿瘤形成的分子机制尚不清楚。方法采用免疫组化方法测定861例结直肠癌标本中ICT1的表达。分析ICT1表达与临床病理参数及生存率的相关性。此外，我们在体外通过MTT、集落形成、流式细胞术和transwell研究了ICT1沉默对结直肠癌细胞增殖和迁移的影响。结果ICT1在人类CRC队列中高表达，ICT1高表达可能导致CRC总生存率降低。同样，ICT1沉默在CRC中通过细胞周期阻滞降低细胞活力，抑制细胞迁移，诱导细胞凋亡。我们进一步揭示了ICT1通过细胞内AMPK、SAPK/JNK和PARP信号通路促进结直肠癌生长的新机制。结论ICT1可作为结直肠癌诊断和治疗的重要靶点。
BackgroundColorectal cancer (CRC) is the third leading cause of death from cancer worldwide. Immature colon carcinoma transcript-1 (ICT1) has been reported to be correlated with lung cancer; however, whether ICT1 is a functional gene in CRC, as well as the molecular mechanism underlying ICT1 mediation of colorectal-tumor formation, remains unknown.MethodsThe expression of ICT1 was firstly determined by using immunohistochemistry in 861 CRC specimens. The correlation of ICT1 expression with clinicopathological parameters and the survival rate was analyzed. Furthermore, we investigated the effect of ICT1 silencing on CRC cell proliferation and migration by MTT, colony formation, flow cytometry, and transwell in vitro.ResultsICT1 is highly expressed in a cohort of human CRCs, and that higher ICT1 expression may lead to reduced overall survival rate of CRC. Likewise, ICT1 silencing lowered the cell viability through cell-cycle arrest, inhibited cell migration, and induced apoptosis in CRC. We further revealed a novel mechanism in which ICT1 promoted CRC growth via the intracellular AMPK, SAPK/JNK, and PARP signaling pathways.ConclusionsOur data showed that ICT1 could be an important target for CRC diagnosis and treatment.