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与肝细胞癌发生相关的五个关键长链非编码RNA的鉴定及功能分析

Identification and functional analysis of five hub lncRNAs associated with oncogenesis of Hepatocellular Carcinoma.

作者信息

Deng Zhaomin, Pu Lu, Ma Yongxin, Jiang Hao

机构信息

Laboratory for Aging and Cancer Research, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu, China.

Laboratory for Aging and Cancer Research, Frontiers Science Center for Disease-related Molecular Network, West China Hospital, Sichuan University, Chengdu, China.

出版信息

PLoS One. 2025 Apr 30;20(4):e0321875. doi: 10.1371/journal.pone.0321875. eCollection 2025.

DOI:10.1371/journal.pone.0321875
PMID:40305510
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12043124/
Abstract

Liver cancer stands as one of the most pervasive and aggressive malignant neoplasms on a global scale, with hepatocellular carcinoma (HCC) accounting for over 90% of primary liver cancer cases. It has been documented that long non-coding RNA (lncRNA) plays a significant role in various pathological contexts and serves as a pivotal determinant in numerous malignancies, including HCC. Leveraging mRNA sequencing data and lncRNA expression profiles from 346 HCC samples and 50 pairs of adjacent normal samples sourced from the TCGA database, a comprehensive bioinformatics analysis was conducted. The dataset was randomly partitioned into a training subset and a validation subset. This rigorous analysis aimed to pinpoint the lncRNAs intricately linked to the oncogenesis of HCC, unveiling distinct expression patterns of these lncRNAs between normal liver and HCC samples across different stages. Moreover, the construction of a lncRNA-mRNA co-expression network led to the identification of five central lncRNA hubs (AC091057, AC099850, AC012073, DDX11-AS1, and AL035461). Subsequently, these five lncRNAs were validated using the independent validation set. In summary, this investigation successfully discerned five lncRNAs closely associated with the oncogenesis of HCC, thereby shedding light on their potential utility as diagnostic or therapeutic targets for this formidable disease.

摘要

肝癌是全球范围内最普遍且侵袭性最强的恶性肿瘤之一,其中肝细胞癌(HCC)占原发性肝癌病例的90%以上。有文献记载,长链非编码RNA(lncRNA)在各种病理情况下发挥着重要作用,并且在包括HCC在内的众多恶性肿瘤中是一个关键决定因素。利用来自TCGA数据库的346例HCC样本和50对相邻正常样本的mRNA测序数据和lncRNA表达谱,进行了全面的生物信息学分析。该数据集被随机分为训练子集和验证子集。这项严谨的分析旨在找出与HCC肿瘤发生密切相关的lncRNA,揭示这些lncRNA在正常肝脏和不同阶段的HCC样本之间的不同表达模式。此外,通过构建lncRNA-mRNA共表达网络,确定了五个核心lncRNA枢纽(AC091057、AC099850、AC012073、DDX11-AS1和AL035461)。随后,使用独立验证集对这五个lncRNA进行了验证。总之,本研究成功识别出五个与HCC肿瘤发生密切相关的lncRNA,从而为它们作为这种严重疾病的诊断或治疗靶点的潜在用途提供了线索。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6731/12043124/9ec3e314303b/pone.0321875.g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6731/12043124/1eefd2e35bd7/pone.0321875.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6731/12043124/6c4045f2bcc9/pone.0321875.g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6731/12043124/215a70e35ab7/pone.0321875.g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6731/12043124/55f10502fe9f/pone.0321875.g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6731/12043124/9ec3e314303b/pone.0321875.g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6731/12043124/1eefd2e35bd7/pone.0321875.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6731/12043124/6c4045f2bcc9/pone.0321875.g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6731/12043124/215a70e35ab7/pone.0321875.g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6731/12043124/55f10502fe9f/pone.0321875.g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6731/12043124/9ec3e314303b/pone.0321875.g005.jpg

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本文引用的文献

1
The interactions between DNA methylation machinery and long non-coding RNAs in tumor progression and drug resistance.DNA 甲基化机制与长链非编码 RNA 在肿瘤进展和耐药中的相互作用。
DNA Repair (Amst). 2023 Aug;128:103526. doi: 10.1016/j.dnarep.2023.103526. Epub 2023 Jun 17.
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Immunotherapy for hepatocellular carcinoma: Current status and future perspectives.肝细胞癌的免疫治疗:现状与展望。
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Evolving therapeutic landscape of advanced hepatocellular carcinoma.
晚期肝细胞癌不断演变的治疗格局。
Nat Rev Gastroenterol Hepatol. 2023 Apr;20(4):203-222. doi: 10.1038/s41575-022-00704-9. Epub 2022 Nov 11.
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DNA methylation fingerprint of hepatocellular carcinoma from tissue and liquid biopsies.肝癌组织和液体活检的 DNA 甲基化指纹图谱。
Sci Rep. 2022 Jul 7;12(1):11512. doi: 10.1038/s41598-022-15058-0.
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Hepatocellular Carcinoma in 2021: An Exhaustive Update.2021年肝细胞癌:详尽的最新进展
Cureus. 2021 Nov 5;13(11):e19274. doi: 10.7759/cureus.19274. eCollection 2021 Nov.
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Hepatocellular carcinoma (HCC): Epidemiology, etiology and molecular classification.肝细胞癌(HCC):流行病学、病因学和分子分类。
Adv Cancer Res. 2021;149:1-61. doi: 10.1016/bs.acr.2020.10.001. Epub 2020 Nov 28.
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A five lncRNA signature for prognosis prediction in hepatocellular carcinoma.一个用于预测肝细胞癌预后的五个长链非编码 RNA 特征。
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Six-long non-coding RNA signature predicts recurrence-free survival in hepatocellular carcinoma.长链非编码 RNA 标志物预测肝细胞癌无复发生存率。
World J Gastroenterol. 2019 Jan 14;25(2):220-232. doi: 10.3748/wjg.v25.i2.220.
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Construction of a long non-coding RNA-associated ceRNA network reveals potential prognostic lncRNA biomarkers in hepatocellular carcinoma.长链非编码RNA相关ceRNA网络的构建揭示了肝细胞癌中潜在的预后lncRNA生物标志物
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