LncRNA CASC9 promotes tumorigenesis by affecting EMT and predicts poor prognosis in esophageal squamous cell cancer
LncRNA CASC9 promotes tumorigenesis by affecting EMT and predicts poor prognosis in esophageal squamous cell cancer
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DOI：
10.26355/eurrev_201801_14191
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发表时间：
2018-01-01
影响因子：
3.3
通讯作者：
Zhang, G. -J.
中科院分区：
文献类型：
--
作者：
Gao, G. -D.;Liu, X. -Y.;Zhang, G. -J.
目的：探讨长链非编码RNA CASC9 （cas9）在食管鳞状细胞癌（ESCC）中的临床意义和生物学功能。患者和方法：采用实时荧光定量PCR （qRT-PCR）检测cas9在ESCC组织和细胞系中的表达。采用受试者工作特征曲线评价cas9的敏感性和特异性。分析cas9水平与患者临床病理因素的相关性。然后采用Kaplan-Meier法和比例风险模型评估生存率。通过细胞计数试剂盒-8 （Cell Counting Kit-8, CCK-8）、迁移和侵袭评估cas9对ESCC细胞的影响。最后用Western blot检测几种EMT标记的表达。结果：我们发现cas9在ESCC细胞系和临床组织中显著上调。cas9水平区分ESCC组织与正常组织，ROC曲线下面积（AUC）为0.813。此外，cas9表达水平与肿瘤分期、淋巴结转移及临床分期之间均有统计学意义。Kaplan-Meier分析显示，高表达的CASC9对总生存期（p = 0.014）和无病生存期（p = 0.0025）有显著影响。此外，在多变量分析中，CASC9表达是总生存期和无病生存期的独立预后指标。体外实验表明，抑制cas9可抑制ESCC的增殖、迁移和侵袭。进一步的机制研究发现，异常的cas9表达可以调节EMT标志物的表达水平。结论：我们的数据强调了cas9作为ESCC的一种新型诊断、预后生物标志物和潜在治疗靶点的关键作用。
OBJECTIVE: The purpose of this study was to explore the clinical significance and biological function of long noncoding RNA CASC9 (CASC9) in esophageal squamous cell carcinoma (ESCC).PATIENTS AND METHODS: Quantitative Real-time PCR (qRT-PCR) was used to determine the expression of CASC9 in ESCC tissues and cell lines. Receiver operating characteristic curves were used to evaluate the sensitivity and specificity of CASC9. The correlation between the CASC9 levels and the clinicopathological factors of the patients was also analyzed. Then, the survival was assessed by the Kaplan-Meier method and proportional hazards model. The effects of CASC9 on ESCC cells were evaluated by Cell Counting Kit-8 (CCK-8), migration and invasion. Finally, several EMT markers expression was detected by Western blot.RESULTS: We found that CASC9 was significantly upregulated in ESCC cell lines and clinical tissues. The CASC9 levels discriminated ESCC tissues from normal tissues with an area under the ROC curve (AUC) of 0.813. In addition, there is statistical significance between CASC9 expression level and tumor stage, lymph nodes metastasis, and clinical stage. Kaplan-Meier analysis indicated that high CASC9 expression had a significant impact on overall survival (p = 0.014) and disease-free survival (p = 0.0025). Moreover, CASC9 expression was an independent prognostic marker of overall survival and disease-free survival in a multivariate analysis. In vitro assay indicated that inhibition of CASC9 could suppress proliferation, migration, and invasion in ESCC. Further mechanistic studies found that aberrant CASC9 expression could modulate the expression levels of markers of EMT.CONCLUSIONS: Our data highlight the pivotal role of CASC9 as a novel diagnostic, prognostic biomarker and a potential therapeutic target of ESCC.