Identification of long noncoding RNA expression profile in oxaliplatin-resistant hepatocellular carcinoma cells.
Identification of long noncoding RNA expression profile in oxaliplatin-resistant hepatocellular carcinoma cells.
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奥沙利铂耐药性肝细胞癌细胞中长非编码 RNA 表达谱的鉴定。
DOI：
10.1016/j.gene.2016.10.008
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发表时间：
2017-01
期刊：
影响因子：
--
通讯作者：
Zheng-Gang Ren
中科院分区：
文献类型：
--
作者：
Xiao-Ying Xie;Yan Wang;Bo-Heng Zhang;Zheng-Gang Ren
肝细胞癌（HCC）是最常见和最恶性的肝癌类型。肝癌的发病率高，化疗耐药是导致肝癌高死亡率的主要原因。最近，长链非编码RNA（lncRNA）的异常表达已被认为是许多类型癌症的主要特征。然而，lncRNA在化疗耐药HCC细胞中的全基因组表达模式和相关功能意义仍然未知。在这项研究中，我们鉴定了120个差异表达的lncRNA，其中61个上调，59个下调。（倍数变化> 2，p < 0.05）沿着的是421个差异表达的mRNA，其中228个上调，193个下调（倍数变化> 2，p < 0.05）。这些信号通路包括p53通路、ErbB通路和MAPK通路。此外，选择16种lncRNA用于用定量PCR验证微阵列结果，并且在qPCR结果和微阵列数据之间鉴定出强相关性。我们首次证明ENST 00000438347、NR_073453和ENST 00000502804在MHCC 97 H-OXA细胞以及化学抗性HCC癌组织中上调。此外，ENST 00000518376的表达与肿瘤的大小和分化程度显著相关。总生存分析显示ENST 00000438347和ENST 00000518376的高表达与HCC患者的不良预后相关。综上所述，我们的结果表明，奥沙利铂耐药HCC的表达谱发生了显著改变，包括lncRNA。而一系列的从头lncRNA在HCC奥沙利铂耐药和HCC进展中起重要作用。
Hepatocellular carcinoma (HCC) is the most prevalent and malignant type of liver cancer. Besides the high incidence, the resistance to chemotherapy is a major problem that leads to the high mortality of HCC. Recently, aberrant expression of long noncoding RNAs (lncRNAs) has been considered as a primary feature of many types of cancer. However, the genome-wide expression pattern and associated functional implications of lncRNAs in chemo-resistant HCC cells remain unknown. In this study, we identified 120 differentially expressed lncRNAs with 61 up-regulated and 59 down-regulated (fold change > 2, p < 0.05) along with 421 differentially expressed mRNAs with 228 up-regulated and 193 down-regulated (fold change > 2, p < 0.05) in oxaliplatin-resistant (MHCC97H-OXA) HCC cells, compared to parental oxaliplatin-sensitive (MHCC97H) by microarray. The underlying pathways were related to cell death, proliferation, cellular response to stimulus, including p53 pathway, ErbB pathway and MAPK pathway. Further, 16 lncRNAs were selected for validation of microarray results with quantitative PCR, and a strong correlation was identified between the qPCR results and microarray data. We demonstrated for the first time that ENST00000438347, NR_073453 and ENST00000502804 were up-regulated in MHCC97H-OXA cells as well as chemo-resistant HCC cancerous tissues. Moreover, the expression of ENST00000518376 was significantly associated with the tumor size and differentiation. Overall survival analysis showed that high expression of ENST00000438347 and ENST00000518376 was associated with poor prognosis in HCC patients. Taken together, our results reveal that the expression profile in oxaliplatin-resistant HCC is significantly altered including lncRNAs. And a series of de novo lncRNAs play important functions in HCC oxaliplatin resistance and HCC progression.
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