Abstract
Hepatitis B virus (HBV)‑related hepatocellular carcinoma (HCC) is a global health problem that accounts for more than half of total liver cancer cases in developing countries. Despite the growing number of researches conducted, the molecular mechanism underlying the development of HCC remains elusive. Long non‑coding RNAs (lncRNAs), which are non‑coding RNAs >200nt in length that were previously considered to be transcriptional noise, have been found to be dysregulated in HBV‑related HCC with the help of high‑throughput omics techniques. Subsequent investigations revealed that aberrant expression of lncRNAs may affect the risk of HBV‑related HCC through diverse mechanisms, including epigenetic silencing of transcriptional activation, alternative splicing, molecular sponging, modulating protein stability, and by serving as precursors of miRNAs. Although the sensitivity and specificity of lncRNAs must be further validated, a number of circulating lncRNAs have been identified as useful biomarkers for HBV‑related HCC. In addition to these findings, recent studies also unveiled that certain genetic polymorphisms in lncRNAs may affect the occurrence and prognosis of HBV‑related HCC. The aim of the present review was to provide an overview of the mechanisms underlying the involvement of lncRNAs in HBV‑related HCC. Subsequently, lncRNAs found to be dysregulated in HBV‑related HCC were focused on and current findings on circulating lncRNAs and their genetic polymorphisms were discussed.
Highlights
ZHANG et al: LncRNAs AND Hepatitis B virus (HBV)-RELATED hepatocellular carcinoma (HCC) and antisense Long non‐coding RNAs (lncRNAs) (Fig. 1) [9]
Several circulating lncRNAs and genetic polymorphisms in lncRNAs are screened out to affect the risk and prognosis of HBV‐related HCC. These studies will hopefully elucidate the mechanism of action of lncRNAs and help in the prevention, diagnosis and treatment of HBV‐related HCC
The findings of these studies are valuable, the functions of a large proportion of lncRNAs dysregulated in HBV‐related HCC remain elusive
Summary
A number of lncRNAs are dysregulated in HBV‐related HCC. As illustrated in Fig. 2, these lncRNAs affect the risk and prognosis of HBV‐related HCC through diverse mechanisms, such as epigenetic silencing, transcriptional activation, alternative splicing regulation, molecular sponging, modulating protein stability, and by serving as precursors for miRNAs (Fig. 2). These lncRNAs affect the risk and prognosis of HBV‐related HCC through diverse mechanisms, such as epigenetic silencing, transcriptional activation, alternative splicing regulation, molecular sponging, modulating protein stability, and by serving as precursors for miRNAs (Fig. 2). These mechanisms will be briefly delineated below. MiR‐374a and miR‐545, located in one of these two clusters, are induced by HBV X protein (HBx) and are upregulated in HBV‐related HCC These two miRNAs are correlated with poor prognosis of HCC patients and promote the proliferation, migration and invasion of HCC cells [41]
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