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 highlights how lncRNAs may help bridge this critical gap by providing new opportunities for earlier detection and more targeted therapeutic strategies.
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.
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.
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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Genes & Diseases publishes rigorously peer-reviewed and high quality original articles and authoritative reviews that focus on the molecular bases of human diseases. Emphasis is placed on hypothesis-driven, mechanistic studies relevant to pathogenesis and/or experimental therapeutics of human diseases. The journal has worldwide authorship, and a broad scope in basic and translational biomedical research of molecular biology, molecular genetics, and cell biology, including but not limited to cell proliferation and apoptosis, signal transduction, stem cell biology, developmental biology, gene regulation and epigenetics, cancer biology, immunity and infection, neuroscience, disease-specific animal models, gene and cell-based therapies, and regenerative medicine.
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Reference
Faisal Mahmood, Maher Un Nisa Awan, Meng-Ting Luo, Xiao Li, Xiao-bin Peng, Jun Xu, Jia Wei, Tai-Cheng Zhou, Current progress and role of lncRNAs in HBV infection and progression of hepatocellular carcinoma, Genes & Diseases, Volume 13, Issue 5, 2026, 101878, https://doi.org/10.1016/j.gendis.2025.101878
Funding
National Foreign Expert Project (China) Y20240212
Leading Talents in Medical Disciplines of Yunnan Province, China (No. D-2024002
Reserve Talents for Middle, Young aged Academic and Technical Leaders in Yunnan Province, China 202205AC160023
The 14th Five-Year Plan Yunnan Provincial Key Clinical Specialty Project - Infectious Diseases Department (China) ZKF2025015
Yunnan Provincial Major Science and Technology Special Project Plan – Biomedicine Special Project (China) 202502AA310011
Yunnan Fundamental Research Projects (China) 202301AT070248
Kunming Medical Joint Project of Yunnan Provincial Department of Science and Technology (China) 202401AY070001-173
Kunming Medical Joint Project of Yunnan Provincial Department of Science and Technology (China) 202501AY070001-216
Kunming Medical Joint Project of Yunnan Provincial Department of Science and Technology (China) 202201AY070001-275
Genes & Diseases