Perspectives on NcRNAs in HBV/cccDNA-driven HCC progression
Abstract Hepatitis B virus (HBV) integration, the HBx protein (and its mutants), and covalently closed circular DNA (cccDNA) are critical for HBV replication, packaging, and transmission to new host cells. Although nucleos(t)ide analogs (NAs) are a class of antiviral drugs that effectively suppress...
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BMC
2025-06-01
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| Series: | Cancer Cell International |
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| Online Access: | https://doi.org/10.1186/s12935-025-03849-0 |
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| author | Yang-Hsiang Lin Ming-Wei Lai Chau-Ting Yeh Wey-Ran Lin |
| author_facet | Yang-Hsiang Lin Ming-Wei Lai Chau-Ting Yeh Wey-Ran Lin |
| author_sort | Yang-Hsiang Lin |
| collection | DOAJ |
| description | Abstract Hepatitis B virus (HBV) integration, the HBx protein (and its mutants), and covalently closed circular DNA (cccDNA) are critical for HBV replication, packaging, and transmission to new host cells. Although nucleos(t)ide analogs (NAs) are a class of antiviral drugs that effectively suppress HBV replication, they do not eliminate cccDNA. This persistent cccDNA, often referred to as an “invisible bullet”, plays a pivotal role not only in the horizontal transmission of HBV but also within the context of hepatocellular carcinoma (HCC). Growing evidence reveals that noncoding RNAs (ncRNAs) are deeply involved in cancer progression, as well as the HBV life cycle and related pathogenesis, including liver inflammation, fibrosis, and HCC. This involvement occurs through various mechanisms, as ncRNAs regulate gene transcription, act as miRNA sponges, modulate signaling pathways, and influence downstream effects. These functions depend on the proper formation of RNA structures, which are critical for maintaining the biological activity of ncRNAs. The structure of RNAs appears to play a pivotal role in their functional capacity. Moreover, both ncRNAs and viral nucleotides contribute to G-quadruplex structure formation, which is essential for the HBV life cycle and cancer progression. In this review, we provide an updated overview of the mechanisms by which key ncRNAs mediate HBV/cccDNA actions in HCC progression and focus on their roles in gene expression and structural formation/modification. |
| format | Article |
| id | doaj-art-85ebaafc27aa4d1f81ed59f023c40438 |
| institution | OA Journals |
| issn | 1475-2867 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | BMC |
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| series | Cancer Cell International |
| spelling | doaj-art-85ebaafc27aa4d1f81ed59f023c404382025-08-20T02:10:35ZengBMCCancer Cell International1475-28672025-06-0125111310.1186/s12935-025-03849-0Perspectives on NcRNAs in HBV/cccDNA-driven HCC progressionYang-Hsiang Lin0Ming-Wei Lai1Chau-Ting Yeh2Wey-Ran Lin3Liver Research Center, Chang Gung Memorial HospitalLiver Research Center, Chang Gung Memorial HospitalLiver Research Center, Chang Gung Memorial HospitalLiver Research Center, Chang Gung Memorial HospitalAbstract Hepatitis B virus (HBV) integration, the HBx protein (and its mutants), and covalently closed circular DNA (cccDNA) are critical for HBV replication, packaging, and transmission to new host cells. Although nucleos(t)ide analogs (NAs) are a class of antiviral drugs that effectively suppress HBV replication, they do not eliminate cccDNA. This persistent cccDNA, often referred to as an “invisible bullet”, plays a pivotal role not only in the horizontal transmission of HBV but also within the context of hepatocellular carcinoma (HCC). Growing evidence reveals that noncoding RNAs (ncRNAs) are deeply involved in cancer progression, as well as the HBV life cycle and related pathogenesis, including liver inflammation, fibrosis, and HCC. This involvement occurs through various mechanisms, as ncRNAs regulate gene transcription, act as miRNA sponges, modulate signaling pathways, and influence downstream effects. These functions depend on the proper formation of RNA structures, which are critical for maintaining the biological activity of ncRNAs. The structure of RNAs appears to play a pivotal role in their functional capacity. Moreover, both ncRNAs and viral nucleotides contribute to G-quadruplex structure formation, which is essential for the HBV life cycle and cancer progression. In this review, we provide an updated overview of the mechanisms by which key ncRNAs mediate HBV/cccDNA actions in HCC progression and focus on their roles in gene expression and structural formation/modification.https://doi.org/10.1186/s12935-025-03849-0HBVHBxCccDNANucleos(t)ide analogueHCCNcRNAs |
| spellingShingle | Yang-Hsiang Lin Ming-Wei Lai Chau-Ting Yeh Wey-Ran Lin Perspectives on NcRNAs in HBV/cccDNA-driven HCC progression Cancer Cell International HBV HBx CccDNA Nucleos(t)ide analogue HCC NcRNAs |
| title | Perspectives on NcRNAs in HBV/cccDNA-driven HCC progression |
| title_full | Perspectives on NcRNAs in HBV/cccDNA-driven HCC progression |
| title_fullStr | Perspectives on NcRNAs in HBV/cccDNA-driven HCC progression |
| title_full_unstemmed | Perspectives on NcRNAs in HBV/cccDNA-driven HCC progression |
| title_short | Perspectives on NcRNAs in HBV/cccDNA-driven HCC progression |
| title_sort | perspectives on ncrnas in hbv cccdna driven hcc progression |
| topic | HBV HBx CccDNA Nucleos(t)ide analogue HCC NcRNAs |
| url | https://doi.org/10.1186/s12935-025-03849-0 |
| work_keys_str_mv | AT yanghsianglin perspectivesonncrnasinhbvcccdnadrivenhccprogression AT mingweilai perspectivesonncrnasinhbvcccdnadrivenhccprogression AT chautingyeh perspectivesonncrnasinhbvcccdnadrivenhccprogression AT weyranlin perspectivesonncrnasinhbvcccdnadrivenhccprogression |