Zhang Haohai, Zhu Chengpei, Zhao Yi, Li Ming, Wu Liangcai, Yang Xiaobo, Wan Xueshuai, Wang Anqiang, Zhang Michael Q, Sang Xinting, Zhao Haitao
Department of Liver Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
School of Medicine, MOE Key Laboratory of Bioinformatics and Bioinformatics Division, Center for Synthetic and System Biology, Tsinghua University, Beijing, China.
Oncotarget. 2015 Dec 22;6(41):43770-8. doi: 10.18632/oncotarget.6087.
Recently, long non-coding RNAs (lncRNAs) were found to be implicated in cancer progression. However, the contributions of lncRNAs to Hepatitis C virus-related hepatocellular carcinoma (HCC) remain largely unknown. Here, we characterized lncRNA expression in 73 tissue samples from several different developmental stages of HCV-related hepatocarcinogenesis by repurposing microarray data sets. We found that the expression of 7 lncRNAs in preneoplastic lesions and HCC was significantly different. Among these significantly differently expressed lncRNAs, the lncRNA LINC01419 transcripts were expressed at higher levels in early stage HCC compared to dysplasia and as compared with early stage HCC, lncRNA AK021443 level increase in advanced stage HCC while lncRNA AF070632 level decrease in advanced stage HCC. Using quantitative real-time reverse-transcription PCR, we validated that LINC01419 was significantly overexpressed in HBV-related and HCV-related HCC when compared with matched non-tumor liver tissues. Moreover, functional predictions suggested that LINC01419 and AK021443 regulate cell cycle genes, whereas AF070632 is associated with cofactor binding, oxidation-reduction and carboxylic acid catabolic process. These findings provide the first large-scale survey of lncRNAs associated with the development of hepatocarcinogenesis and may offer new diagnostic biomarkers and therapeutic targets for HCV-related HCC.
最近，人们发现长链非编码RNA（lncRNAs）与癌症进展有关。然而，lncRNAs在丙型肝炎病毒相关肝细胞癌（HCC）中的作用仍 largely未知。在此，我们通过重新利用微阵列数据集，对来自HCV相关肝癌发生几个不同发育阶段的73个组织样本中的lncRNA表达进行了表征。我们发现7种lncRNAs在癌前病变和HCC中的表达存在显著差异。在这些表达有显著差异的lncRNAs中，lncRNA LINC01419转录本在早期HCC中的表达水平高于发育异常，与早期HCC相比，lncRNA AK021443在晚期HCC中的水平升高，而lncRNA AF070632在晚期HCC中的水平降低。通过定量实时逆转录PCR，我们验证了与匹配的非肿瘤肝组织相比，LINC01419在HBV相关和HCV相关的HCC中显著过表达。此外，功能预测表明LINC01419和AK021443调节细胞周期基因，而AF070632与辅因子结合、氧化还原和羧酸分解代谢过程相关。这些发现首次对与肝癌发生发展相关的lncRNAs进行了大规模调查，并可能为HCV相关的HCC提供新的诊断生物标志物和治疗靶点。
