A growing body of evidence is highlighting the pivotal role of long non-coding RNAs (lncRNAs) in the progression of hepatitis B virus (HBV) infection and the development of hepatocellular carcinoma (HCC), the most common form of primary liver cancer. A new review brings together current knowledge on how these previously overlooked molecules are shaping the future of diagnosis, prognosis, and treatment in HBV-associated liver disease.
HBV remains a major global health challenge, affecting hundreds of millions of people worldwide and contributing significantly to the burden of liver cancer. While antiviral therapies can help control infection, chronic HBV infection continues to be a leading cause of HCC, a disease often diagnosed at advanced stages when treatment options are limited. The review, published in Genes & Diseases, highlights how lncRNAs may help bridge this critical gap by providing new opportunities for earlier detection and more targeted therapeutic strategies.
Long non-coding RNAs
Unlike protein-coding genes, lncRNAs do not produce proteins but instead act as powerful regulators of cellular activity. They influence gene expression, immune responses, cell growth, inflammation, and programmed cell death.
During HBV infection, many lncRNAs become abnormally regulated, affecting both viral activity and the biological pathways that drive cancer development. Several of these molecules are directly influenced by the viral HBx protein, a key factor in HBV-related liver disease progression.
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The review describes how specific lncRNAs contribute to tumor growth, invasion, metastasis, and immune evasion. Molecules such as HULC, HOTAIR, UCA1, and LINC00152 have emerged as important drivers of cancer-related pathways, while others, including MEG3 and DREH, appear to act as natural tumor suppressors.
Understanding these molecular networks could provide valuable insights into why some HBV infections progress to cancer while others do not.
Non-invasive biomarkers
One of the most promising findings is the potential use of circulating lncRNAs as non-invasive biomarkers. Detectable in blood samples, these molecules may help identify liver cancer earlier and more accurately than current approaches.
Combining lncRNA measurements with existing clinical markers could significantly improve diagnostic performance and help clinicians monitor disease progression and treatment response.
Advances in RNA sequencing, CRISPR-based technologies, and high-throughput genomic tools are accelerating the discovery of new lncRNAs and clarifying their biological functions. Although challenges remain, including low expression levels and the complexity of lncRNA regulation, these molecules are increasingly recognized as important players in both viral infection and cancer biology.
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