Long noncoding RNA CCHE1 indicates a poor prognosis of hepatocellular carcinoma and promotes carcinogenesis via activation of the ERK/MAPK pathway
Long noncoding RNA CCHE1 indicates a poor prognosis of hepatocellular carcinoma and promotes carcinogenesis via activation of the ERK/MAPK pathway
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长链非编码RNA CCHE1表明肝细胞癌预后不良，并通过激活ERK/MAPK通路促进癌变
DOI：
10.1016/j.biopha.2016.06.056
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发表时间：
2016-10-01
影响因子：
7.5
通讯作者：
Fan, Hong
中科院分区：
文献类型：
--
作者：
Peng, Wei;Fan, Hong
肝细胞癌（HCC）患者的生存率仍然很低，这在很大程度上归因于活跃的癌变。越来越多的证据表明，长链非编码rna （lncRNAs）可能在癌症生物学中发挥关键作用。然而，CCHE1在HCC癌变中的临床价值和生物学意义仍有待发现。采用qRT-PCR分析了112例HCC组织和细胞系中CCHE1的表达。CCHE1的高表达与肿瘤数量、肿瘤大小、TNM分期有显著相关性。多变量分析显示，CCHE1表达是总生存率的独立预测因子。MTT法检测CCHE1对细胞增殖的影响，流式细胞术检测细胞凋亡。进一步的实验表明，CCHE1敲低可显著促进生长阻滞和细胞凋亡。重要的是，我们进一步证实，在CCHE1敲低后，我们发现HCC细胞中的ERK/MAPK通路失活。据我们所知，这是首次报道CCHE1在HCC进展中的作用和机制。总之，这些结果表明lncRNA CCHE1可能作为人类HCC新疗法的候选预后生物标志物和靶点。(C) 2016 Elsevier Masson SAS。版权所有。
Survival of patients with hepatocellular carcinoma (HCC) remains poor, which is largely attributed to active carcinogenesis. Accumulating evidence implies that long noncoding RNAs (lncRNAs) could play a pivotal role in cancer biology. However, the clinical valueand biological significance of CCHE1 in HCC carcinogenesis remains to be discovered. Expression of CCHE1 was analyzed in 112 HCC tissues and cell lines by qRT-PCR. The higher expression of CCHE1 was significantly correlated with tumor number, tumor size and TNM stage. Multivariate analyses revealed that CCHE1 expression served as an independent predictor for overall survival. Moreover, the effect of CCHE1 on proliferation was evaluated by MTT assays, and cell apoptosis was detected by flow-cytometric analysis. Further experiments demonstrated that CCHE1 knockdown significantly promoted growth arrest and cell apoptosis. Importantly, we further confirmed that ERK/MAPK pathway was found to be inactivated in the HCC cells after CCHE1 knockdown. To our knowledge, this is the first report showed that the role and the mechanism of CCHE1 in the progression of HCC. Together, these results suggest that lncRNA CCHE1 may serve as a candidate prognostic biomarker and target for new therapies in human HCC. (C) 2016 Elsevier Masson SAS. All rights reserved.