Zhu Hua-Qiang, Zhou Xu, Chang Hong, Li Hong-Guang, Liu Fang-Feng, Ma Chao-Qun, Lu Jun
Department of Hepatobiliary Surgery, Provincial Hospital Affiliated to Shandong University, Jinan, Shandong Province, China E-mail :
Asian Pac J Cancer Prev. 2015;16(13):5181-5. doi: 10.7314/apjcp.2015.16.13.5181.
CCAT1 has been reported to be linked with pathogenesis of malignancies including colon cancer and gastric cancer. However, the regulatory effect of CCAT1 in hepatocellular carcinoma (HCC) remains unclear. The purpose of this research was to identify any role of CCAT1 in the progression of HCC.
Real time-PCR was performed to test the relative expression of CCAT1 in HCC tissues. A computation screen of CCAT1 promoter was conducted to search for transcription-factor-binding sites. The association of c-Myc with CCAT1 promoter in vivo was tested by Pearson correlation analysis and chromatin immunoprecipitation assay. Additionally, Kaplan-Meier analysis and Cox proportional hazards analyses were performed.
c-Myc directly binds to the E-box element in the promoter region of CCAT, and when ectopically expressed increases promoter activity and expression of CCAT1. Moreover, Kaplan-Meier analysis demonstrated that the patients with low expression of CCAT1 demonstrated better overall and relapse-free survival compared with the high expression group. Cox proportional hazards analyses showed that CCAT1 expression was an independent prognostic factor for HCC patients.
The findings demonstrated CCAT1, acting as a potential biomarker in predicting the prognosis of HCC, is regulated by c-Myc.
据报道,CCAT1与包括结肠癌和胃癌在内的恶性肿瘤发病机制有关。然而,CCAT1在肝细胞癌(HCC)中的调节作用仍不清楚。本研究的目的是确定CCAT1在HCC进展中的作用。
采用实时定量PCR检测CCAT1在HCC组织中的相对表达。对CCAT1启动子进行计算筛选以寻找转录因子结合位点。通过Pearson相关分析和染色质免疫沉淀试验检测体内c-Myc与CCAT1启动子的关联。此外,还进行了Kaplan-Meier分析和Cox比例风险分析。
c-Myc直接结合CCAT启动子区域的E-box元件,异位表达时可增加启动子活性和CCAT1的表达。此外,Kaplan-Meier分析表明,与高表达组相比,CCAT1低表达的患者总生存期和无复发生存期更好。Cox比例风险分析表明,CCAT1表达是HCC患者的独立预后因素。
研究结果表明,CCAT1作为预测HCC预后的潜在生物标志物,受c-Myc调控。