长读测序揭示了HBV整合模式和对早期发生的肝细胞癌的瘤性影响
Yao Wang1,2, Dong Yu3, Yue Mei3
1Center for Reproductive Medicine, Changhai Hospital, Naval Medical University, Shanghai, China 200433.
Genome research
|September 16, 2025
概括
乙型肝炎病毒 (HBV) 集成驱动肝癌 (HCC) 通过引起大基因组变化和改变基因表达. 一种特定的HBV增强剂 (HBV-Enh I) 经常集成,并且可能是治疗点.
科学领域:
- 基因组学就是基因组学.
- 病毒学 病毒学
- 在瘤学瘤学.
背景情况:
- 乙型肝炎病毒 (HBV) 整合是已知的肝细胞癌 (HCC) 的驱动因素.
- 由于检测和样本限制,HBV整合的精确瘤机制尚未完全理解.
研究的目的:
- 在基因组和转录组层面全面描述HBV整合事件.
- 阐明HBV整合对HCC的结构变异 (SVs) 和基因表达的调节效应.
- 确定与HBV整合相关的潜在治疗点.
主要方法:
- 牛津纳米孔技术 (ONT) 全基因组测序和全长转录组测序.
- 双露西法酶测定和基于细胞的实验用于功能验证.
主要成果:
- 集成的HBV序列形成了长的结合体,驱动了染色体间和染色体内重组.
- 综合HBV增强剂I (HBV-Enh I) 在大多数瘤组织中被发现,与异常基因表达相关.
- 结合HBV诱导瘤性SVs (例如,MYC放大,NAV2删除) 和调制基因表达,包括MYOCD过度表达,促进HCC细胞迁移和入侵.
结论:
- 乙型肝炎病毒的整合是大规模基因组 SVs 和 HCC 中的转录组失调的主要驱动因素.
- HBV-Enh I 经常被整合到 HCC 中,并且在异常基因表达中起着关键作用,这表明它是潜在的治疗标.
更多相关视频
09:35Development of a Hepatitis B Virus Reporter System to Monitor the Early Stages of the Replication Cycle
Published on: February 1, 2017
13.9K
10:37Analysis of HBV-Specific CD4 T-cell Responses and Identification of HLA-DR-Restricted CD4 T-Cell Epitopes Based on a Peptide Matrix
Published on: October 20, 2021
3.4K
相关概念视频
Non-LTR Retrotransposons
13.2K
As the name suggests, non-LTR retrotransposons lack the long terminal repeats characteristic of the LTR retrotransposons. Additionally, both LTR and non-LTR retrotransposons use distinct mechanisms of mobilization. Non-LTR retrotransposons are further divided into two classes - Long interspersed nuclear elements (LINEs) and short interspersed nuclear elements (SINEs), both of which occur abundantly in most mammals, including humans. Some of the active non-LTR retrotransposons in humans are L1...
13.2K
Mechanisms of Retrovirus-induced Cancers
6.9K
Retroviruses are RNA viruses that have been shown to cause cancers in diverse species, including chickens, mice, cats, and monkeys. The RNA genomes of these viruses are first reverse-transcribed into single and then double-stranded DNA (dsDNA) copies. This dsDNA called proviral DNA then integrates into the host genome. Subsequently, the host cell transcribes the proviral DNA in concert with the chromosomal DNA. This leads to the production of viral RNA and proteins that assemble at the host...
6.9K
Viruses with RNA Genomes
833
RNA viruses are categorized into positive-strand, negative-strand, or double-stranded groups based on their genomic structure and replication mechanisms. This classification dictates how they exploit host cellular machinery for protein synthesis and replication. Some RNA viruses also utilize reverse transcription as part of their life cycle, further diversifying their replication strategies.Positive-Strand RNA VirusesPositive-strand RNA viruses have genomes that function directly as messenger...
833
Next-generation Sequencing
97.8K
The first human genome sequencing project cost $2.7 billion and was declared complete in 2003, after 15 years of international cooperation and collaboration between several research teams and funding agencies. Today, with the advent of next-generation sequencing technologies, the cost and time of sequencing a human genome have dropped over 100 fold.
Next-Generation Sequencing Methods
Although all next-generation methods use different technologies, they all share a set of standard features....
Next-Generation Sequencing Methods
Although all next-generation methods use different technologies, they all share a set of standard features....
97.8K
Rous Sarcoma Virus (RSV) and Cancer
6.2K
Rous Sarcoma virus or RSV was discovered by F. Peyton Rous in the year 1911 as a filterable transmissible agent that could cause tumors in chickens. He won a Nobel Prize for this discovery in 1966. His experiments clearly demonstrated that some cancers could be caused by infectious agents and led to the discovery of many more cancer-causing viruses in animals as well as humans.
RSV is a retrovirus that contains two copies of a plus-strand RNA genome. Its genome consists of four main open...
RSV is a retrovirus that contains two copies of a plus-strand RNA genome. Its genome consists of four main open...
6.2K
Leaky Scanning
5.6K
During most eukaryotic translation processes, the small 40S ribosome subunit scans an mRNA from its 5' end until it encounters the first start AUG codon. The large 60S ribosomal subunit then joins the smaller one to initiate protein synthesis. The location of the translation initiation is largely determined by the nucleotides near the start codon as there may be multiple translation initiation sites present on the mRNA. Marilyn Kozak discovered that the sequence RCCAUGG (where R...
5.6K
