Abstract
Hepatocellular carcinoma (HCC) is one of the most common kinds of malignancies and is closely correlated with hepatitis B virus (HBV) infection. Recent evidence has proved that long non-coding RNAs (lncRNAs) are implicated in development and progression of cancer. However, the contributions of lncRNAs to HBV-related HCC remain largely unknown. Here, we comprehensively investigated lncRNA expression profiles in HBV-related HCC by annotating and analyzing microarray datasets. By analyzing 42 HCC tissue samples with different etiology (HBV-related, alcohol-related, and primary HCC) and 15 normal liver tissues, we identified 182 lncRNAs that were specifically differentially expressed in HBV-related HCC, namely HBV-related HCC specific lncRNAs(HH-lncRNAs). Using an online function annotation tool, we found these HH-lncRNAs were associated many oncogenes and immunity related biological processes. 6 candidate HH-lncRNAs were selected and further validated by quantitative real-time PCR analysis in a cohort of HCC tissue samples. Function of a candidate HH-lncRNAs, BAIAP2-AS1, was further predicted by co-expression network and gene set enrichment analysis. These findings provide insights into HH-lncRNAs and offer resource for further search of biomarkers and therapeutic targets of HBV-related HCC.
Highlights
Hepatocellular carcinoma (HCC) is one of the most common malignant tumors and currently ranks the third course of cancer-related death [1]
By analyzing 42 HCC tissue samples with different etiology (HBV-related, alcoholrelated, and primary HCC) and 15 normal liver tissues, we identified 182 long non-coding RNAs (lncRNAs) that were differentially expressed in hepatitis B virus (HBV)-related HCC, namely HBV-related HCC specific lncRNAs(HH-lncRNAs)
Probe sets of human genome U133 (HG U133) Plus2.0 microarray were annotated by blasting with probe sequences with lncRNA transcripts from RefSeq database
Summary
Hepatocellular carcinoma (HCC) is one of the most common malignant tumors and currently ranks the third course of cancer-related death [1]. The geographic distribution of chronic HBV infection rates and HCC are highly similar [3]. About 90% of human genome is actively transcribed, yielding an extraordinary amount of RNA transcripts without protein-coding capacity [5]. Long non-coding RNA (lncRNA) is an important kind of non-coding RNA transcripts that range from 200nt to 100kb without protein-coding capacity [6, 7]. A novel lncRNA, HULC is upregulated in HCC compared with normal tissues and the expression level of HULC is correlated HBV infection status [17]. HULC could potentially be a biomarker since HULC can be detected in both blood and tumor tissues of HCC patients [18]
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