Long non-coding RNA expression profiles of hepatitis C virus-related dysplasia and hepatocellular carcinoma
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Haohai Zhang1,*, Chengpei Zhu1,*, Yi Zhao2,*, Ming Li3, Liangcai Wu1, Xiaobo Yang1, Xueshuai Wan1, Anqiang Wang1, Michael Q. Zhang1,2, Xinting Sang1, Haitao Zhao1
1Department of Liver Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
2School of Medicine, MOE Key Laboratory of Bioinformatics and Bioinformatics Division, Center for Synthetic and System Biology, Tsinghua University, Beijing, China
3Key Laboratory of Intelligent Information Processing, Institute of Computing Technology, Chinese Academy of Sciences, Beijing, China
*These authors have contributed equally to this work
Haitao Zhao, e-mail: [email protected]
Michael Q. Zhang, e-mail: [email protected]
Xinting Sang, e-mail: [email protected]
Keywords: long non-coding RNAs, hepatitis C virus-related HCC, hepatocarcinogenic process, biomarkers
Received: July 07, 2015 Accepted: October 15, 2015 Published: October 26, 2015
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.
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