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肝细胞癌中侵袭和转移相关的长链非编码RNA表达谱

Invasion and metastasis-related long noncoding RNA expression profiles in hepatocellular carcinoma.

作者信息

Gao Yunzhen, Chen Geng, Zeng Yongyi, Zeng Jinhua, Lin Minjie, Liu Xiaolong, Liu Jingfeng

机构信息

The United Innovation of Mengchao Hepatobiliary Technology Key Laboratory of Fujian Province, Mengchao Hepatobiliary Hospital of Fujian Medical University, Xihong Road 312, Fuzhou, 350025, Fujian Province, People's Republic of China.

The Liver Center of Fujian Province, Fujian Medical University, Fuzhou, 350025, People's Republic of China.

出版信息

Tumour Biol. 2015 Sep;36(10):7409-22. doi: 10.1007/s13277-015-3408-0. Epub 2015 Apr 22.

Abstract

Recurrence, invasion, and metastasis are the major reasons of the low 5-year survival of hepatocellular carcinoma. However, the mechanisms of recurrence, invasion, and metastasis are still poll understood. Long noncoding RNAs (LncRNAs, >200 nt) have been demonstrated to play important roles in both tumor suppressive and oncogenic signaling pathways. Here, we employed the LncRNAs microarray technology to study the LncRNAs expression profiles at genome-wide in hepatocellular carcinoma (HCC) tissue samples with early recurrence (less than 1 year, with invasion and metastasis out of liver) and late recurrence (longer than 2 years, without invasion and metastasis out of liver), which had different recurrent/metastatic potentials, by using normal liver tissue as control to screen the dysregulated LncRNAs which are potentially involved in the recurrence, invasion, and metastasis process of HCC. Overall, 1170 LncRNAs were identified to differentially expressed between the early and late recurrence samples. These differentially expressed LncRNAs were further characterized by integrating examination of genomic context, co-expression network analysis, and gene ontology (GO) enrichment of their associated protein-coding genes. Furthermore, 15 LncRNAs selected randomly from top 50 differentially expressed LncRNAs were validated by quantitative PCR (qPCR) in cell lines MHCC97H and MHCC97L, which have exactly the same genetic background but with different invasion potentials. Meanwhile, the prognostic potential of three verified LncRNAs at cell line level was further validated in 59 HCC samples. Therefore, our results demonstrated that the aberrant expression of LncRNAs might be responsible for the HCC invasion and metastasis and provide fundamental information for further study the LncRNAs involved molecular mechanisms of the invasion and metastasis of HCC.

摘要

复发、侵袭和转移是肝细胞癌5年生存率较低的主要原因。然而,复发、侵袭和转移的机制仍未完全明确。长链非编码RNA(LncRNAs,>200 nt)已被证明在肿瘤抑制和致癌信号通路中均发挥重要作用。在此,我们采用LncRNAs微阵列技术,以正常肝组织为对照,研究具有不同复发/转移潜能的早期复发(小于1年,伴有肝外侵袭和转移)和晚期复发(大于2年,无肝外侵袭和转移)的肝细胞癌(HCC)组织样本全基因组范围内的LncRNAs表达谱,以筛选可能参与HCC复发、侵袭和转移过程的失调LncRNAs。总体而言,共鉴定出1170个LncRNAs在早期和晚期复发样本之间差异表达。通过整合基因组背景检查、共表达网络分析及其相关蛋白质编码基因的基因本体(GO)富集分析,对这些差异表达的LncRNAs进行了进一步表征。此外,从50个差异表达最高的LncRNAs中随机选择15个LncRNAs,在具有完全相同遗传背景但侵袭潜能不同的细胞系MHCC97H和MHCC97L中通过定量PCR(qPCR)进行验证。同时,在59个HCC样本中进一步验证了3个已验证的LncRNAs在细胞系水平的预后潜能。因此,我们的结果表明,LncRNAs的异常表达可能与HCC的侵袭和转移有关,并为进一步研究参与HCC侵袭和转移分子机制的LncRNAs提供了基础信息。

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