Roles of long noncoding RNAs in hepatocellular carcinoma

doi:10.1016/j.virusres.2016.06.008

Virus Research

Volume 223, 2 September 2016, Pages 131-139

https://doi.org/10.1016/j.virusres.2016.06.008 Get rights and content

Highlights

•
In this review, we focused on functional roles of lncRNAs in HBV and HCV related HCC.
•
Through discussing the mechanism of lncRNA in virus-induced HCC, we could better understand the role of lncRNAs in hepatocarcinogenesis and identify new therapeutic targets and diagnostic markers for HCC.

Abstract

Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide with high prevalence and lethality. Hepatitis B virus (HBV) and Hepatitis C virus (HCV) infection are the major risk factors for HCC. Long noncoding RNAs (lncRNAs) are involved in diverse biological processes, and aberrant lncRNA expression is relevant to many human diseases including HCC. Although many researches on HCC have been reported and lncRNAs roles in carcinogenesis have been highlighted recently, reports on roles of lncRNAs in HBV/HCV-induced HCC are limited. In this review, we concentrate on recent progress regarding the functional roles of lncRNAs in HCC and HBV/HCV-related HCC.

Section snippets

LncRNA

Genome Tiling Arrays indicated that protein-coding sequences only constitute a small part of the genome transcripts, the majority of human genome transcripts are non-coding RNAs (ncRNA), which used to be considered as transcriptional noise (Bertone et al., 2004, The FANTOM Consortium et al., 2005, Ponjavic and Ponting, 2007, Ponting et al., 2009, Chen et al., 2013). Recently, an increasing number of studies show that ncRNAs are not transcriptional noise but play important roles in many

LncRNAs in HCC

HCC is the fifth most common cancer and the third leading cause of cancer death worldwide. More than 80% of HCC cases occur in sub-Saharan Africa and Southeast Asia. Specifically, patients from China account for more than 50% of the world’s cases (Hashem EL-Serag and Lenhard Rudolph, 2007, Ferlay et al., 2015). In the United States, HCC is the fastest growing cause of cancer-related death in men (Yang and Roberts, 2010). Surgical resection is a potentially curative treatment for HCC. However,

LncRNAs in HBV related HCC

About three-quarters of HCCs are attributed to chronic hepatitis B virus (HBV) and hepatitis C virus (HCV) infections (Yang and Roberts, 2010, Perz et al., 2006). Chronic HBV infection accounts for approximately 50% of all cases of hepatocellular carcinoma and virtually all childhood cases worldwide (Hashem El-Serag, 2011). There is a heavy burden of HCC in developing countries, where chronic HBV infection is the main risk factor (Alan Venook et al., 2010). The HBV genome is a partially

LncRNAs in HCV related HCC

HCV infection is a major risk factor for the development of HCC, with high promotion of fibrosis and cirrhosis (Hashem EL-Serag and Lenhard Rudolph, 2007, Hoshida et al., 2014, Mitchell et al., 2015). In the United States and Europe, HCV infection is the leading cause of HCC (Llovet et al., 2003). Presently, only a few studies have focused on lncRNAs specific to HCV-induced HCC.

In different developmental stages of HCV-related HCC, Zhang et al. found lncRNA LINC01419 expression was significantly

Conclusion

As we summarized and discussed in this review, lncRNAs act as important regulators of HCC progression [Table 1], by regulating tumor-suppressor and oncogenetic pathways. The functional characterization of HBV/HCV-associated HCC lncRNAs has allowed investigators to obtain a more comprehensive understanding of hepatocarcinogenesis [Table 2, Table 3]. A better understanding of the molecular mechanisms underlying lncRNA-mediated tumorigenesis may help to raise the potential possibility for their

Competing interests

The authors declare that they have no competing interests.

Authors’ contributions

LS carried out manuscript writing. FP collected the literature. YT modified the manuscript. XF conceived of the review. NL designed modified the manuscript. All authors read and approved the final manuscript.

Acknowledgements

This work was supported by grants form Special National International Technology Cooperation of China (No.2015DFA31490), Natural Science Foundation of Hunan Province, China (No.11JJ6072), and Science and Technology Commission of Hunan province, China (No. 2014SK4066).

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Despite an improved OS among patients with HCC from advancements in surgical techniques, liver-directed and systemic therapy, the 5-year OS remains low, at 18%, highlighting the need for novel therapies.21 In recent years, a series of investigations have deepened the understanding of the crucial roles of lncRNAs in hepatocarcinogenesis and progression.22–24 Noncoding RNAs >200 nucleotides are defined as lncRNAs.
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¹: These authors contributed equally to this work.

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Roles of long noncoding RNAs in hepatocellular carcinoma

Highlights

Abstract

Section snippets

LncRNA

LncRNAs in HCC

LncRNAs in HBV related HCC

LncRNAs in HCV related HCC

Conclusion

Competing interests

Authors’ contributions

Acknowledgements

Cancer Cell

Neoplasia

Biol. Chem.

Cancer Lett.

Cell Stem Cell

J. Hepatol.

Cancer Lett.

Cancer Lett.

Cancer Cell

J. Hepatol.

Lancet

Eur. Urol.

Curr. Opin. Virol.

Gastroenterology

J. Hepatol.

Cell

Curr. Opin. Virol.

Immunity

Cancer Lett.

Mol. Cell

Autoimmun. Rev.

Mol. Cell

Cancer Lett.

Cancer Cell

Phytomedicine

The incidence and epidemiology of hepatocellular carcinoma: a global and regional perspective

Oncologist

Michael snyder global identification of huma transcribed sequences with genome tiling arrays

Science

Tushar Patel Expression and functional role of a transcribed noncoding RNA with an ultraconserved element in hepatocellular carcinoma

Proc. Natl. Acad. Sci. U. S. A.

microRNA-29 can regulate expression of the long non-coding RNA gene MEG3 in hepatocellular cancer

Oncogene

Armored long non-coding RNA MEG3 targeting EGFR based on recombinant MS2 bacteriophage virus-like particles against hepatocellular carcinoma

Oncotarget

Qinghua Cui LncRNADisease: a database for long-non-coding RNA-associated diseases

Nucleic Acids Res.

evaluation of antimetastatic effect of lncRNA-ATB siRNA delivered using ultrasound-targeted microbubble destruction

DNA Cell Biol.

Long noncoding RNA HULC modulates abnormal lipid metabolism in hepatoma cells through an miR-9-Mediated RXRA signaling pathway

Cancer Res.

Evidence of RNAi in humans from systemically administered siRNA via targeted nanoparticles

Nature

Long non-coding RNAs as emerging regulators of differentiation, development, and disease

Transcription

Non-coding RNAs in human disease

Nat. Rev. Genet.

Processing of snoRNAs as a new source of regulatory non-coding RNAs: snoRNA fragments form a new class of functional RNAs

Bioessays

Long non-coding RNAs: new players in cell differentiation and development

Nat. Rev. Genet.

Long non-coding RNA HOTTIP is frequently up-regulated in hepatocellular carcinoma and is targeted by tumour suppressive miR-125b

Liver Int.

Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012

Int. J. Cancer

MiRNA-192 and miRNA-204 directly suppress lncRNA HOTTIP and interrupt GLS1-Mediated glutaminolysis in hepatocellular carcinoma

PLoS Genet.

Long noncoding RNA HOTAIR reprograms chromatin state to promote cancer metastasis

Nature

The hallmarks of cancer A long non-coding RNA point of view

RNA Biol.

Sven diederichs posttranscriptional destabilization of the liver-Specific long noncoding RNA HULC by the IGF2 mRNA-Binding protein 1 (IGF2BP1)

Hepatology