Abstract
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.
Highlights
Hepatocellular carcinoma (HCC) is one of the most frequently diagnosed cancers in the world and is the second leading cause of cancer-related deaths worldwide [1]
Of the publicly available gene expression microarray data sets, we focused on repurposing microarray data sets comprising 75 samples that represent all stages of hepatitis C virus (HCV)-induced HCC
With the exception often healthy liver tissue samples, the samples used in this microarray dataset were derived from patients with hepatitis C virus infection, which is the leading cause of HCC in the United States and Europe [4]
Summary
Hepatocellular carcinoma (HCC) is one of the most frequently diagnosed cancers in the world and is the second leading cause of cancer-related deaths worldwide [1]. Hepatocellular carcinoma pathogenesis is a slow process that may take more than 30 years to develop after the initial diagnosis of chronic infection with HBV or HCV. An investigation of the molecular events across this slow process could identify crucial genes involved in HCC pathogenesis [6,7,8]. Such genes are potential biomarkers for the early detection of HCC [8, 9] or for predicting the prognosis of patients with HCC [10,11,12]. In addition to approximately 20,000 protein-coding genes and encoded small RNA molecules, the human transcriptome comprises a large number of long, nonproteincoding RNAs (long noncoding RNAs; lncRNAs) [13]
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