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探讨 LncRNA CASC15 通过 miRNA 影响肝细胞癌的机制。

Exploring the mechanism of LncRNA CASC15 affecting hepatocellular carcinoma through miRNA.

机构信息

Department of Hepatobiliary Surgery, Tangshan Central Hospital, Hebei Province, China.

Department of Otolaryngology, Qian 'an People's Hospital, Hebei Province, China.

出版信息

Medicine (Baltimore). 2024 Feb 2;103(5):e35859. doi: 10.1097/MD.0000000000035859.

DOI:10.1097/MD.0000000000035859
PMID:38306545
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10843454/
Abstract

This study aimed to determine the potential mechanisms through which long noncoding (Lnc) RNA cancer susceptibility candidate 15 (CASC15) affects hepatocellular carcinoma (HCC). We retrieved HCC RNA-seq and clinical information from the UCSC Xena database. The differential expression (DE) of CASC15 was detected. Overall survival was analyzed using Kaplan-Meier (K-M) curves. Molecular function and signaling pathways affected by CASC15 were determined using Gene Set Enrichment Analysis. Associations between CASC15 and the HCC microenvironment were investigated using immuno-infiltration assays. A differential CASC15-miRNA-mRNA network and HCC-specific CASC15-miRNA-mRNA ceRNA network were constructed. The overexpression of CASC15 in HCC tissues was associated with histological grade, clinical stage, pathological T stage, poor survival, more complex immune cell components, and 12 immune checkpoints. We identified 27 DE miRNAs and 270 DE mRNAs in the differential CASC15-miRNA-mRNA network, and 10 key genes that were enriched in 12 cancer-related signaling pathways. Extraction of the HCC-specific CASC15-miRNA-mRNA network revealed that IGF1R, MET, and KRAS were associated with HCC progression and occurrence. Our bioinformatic findings confirmed that CASC15 is a promising prognostic biomarker for HCC, and elevated levels in HCC are associated with the tumor microenvironment. We also constructed a disease-specific CASC15-miRNA-mRNA regulatory ceRNA network that provides a new perspective for the precise indexing of patients with elevated levels of CASC15.

摘要

本研究旨在确定长链非编码 (Lnc) RNA 癌症易感性候选基因 15 (CASC15) 影响肝细胞癌 (HCC) 的潜在机制。我们从 UCSC Xena 数据库中检索了 HCC RNA-seq 和临床信息。检测 CASC15 的差异表达 (DE)。使用 Kaplan-Meier (K-M) 曲线分析总生存期。使用基因集富集分析确定 CASC15 影响的分子功能和信号通路。使用免疫浸润测定法研究 CASC15 与 HCC 微环境之间的关联。构建差异 CASC15-miRNA-mRNA 网络和 HCC 特异性 CASC15-miRNA-mRNA ceRNA 网络。HCC 组织中 CASC15 的过表达与组织学分级、临床分期、病理 T 分期、不良预后、更复杂的免疫细胞成分和 12 个免疫检查点有关。我们在差异 CASC15-miRNA-mRNA 网络中鉴定出 27 个 DE miRNAs 和 270 个 DE mRNAs,以及在 12 个癌症相关信号通路中富集的 10 个关键基因。提取 HCC 特异性 CASC15-miRNA-mRNA 网络显示 IGF1R、MET 和 KRAS 与 HCC 进展和发生有关。我们的生物信息学发现证实 CASC15 是 HCC 有前途的预后生物标志物,HCC 中的高水平与肿瘤微环境有关。我们还构建了疾病特异性 CASC15-miRNA-mRNA 调节 ceRNA 网络,为精确标记 CASC15 水平升高的患者提供了新视角。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/39af/10843454/36609a96a7e0/medi-103-e35859-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/39af/10843454/8d1b38b0f1ff/medi-103-e35859-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/39af/10843454/746060cb2dc9/medi-103-e35859-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/39af/10843454/5f1df7036d08/medi-103-e35859-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/39af/10843454/0923a5aec555/medi-103-e35859-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/39af/10843454/2f68ce5a6cd5/medi-103-e35859-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/39af/10843454/36609a96a7e0/medi-103-e35859-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/39af/10843454/8d1b38b0f1ff/medi-103-e35859-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/39af/10843454/746060cb2dc9/medi-103-e35859-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/39af/10843454/5f1df7036d08/medi-103-e35859-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/39af/10843454/0923a5aec555/medi-103-e35859-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/39af/10843454/2f68ce5a6cd5/medi-103-e35859-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/39af/10843454/36609a96a7e0/medi-103-e35859-g006.jpg

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