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鉴定 EMT 相关的长链非编码 RNA 特征和 LINC01116 作为肝癌中的免疫相关致癌基因。

Identification of an EMT-related lncRNA signature and LINC01116 as an immune-related oncogene in hepatocellular carcinoma.

机构信息

Hepatic Surgery Center, Tongji Medical College, Tongji Hospital, Huazhong University of Science and Technology, Wuhan, China.

Hubei Key Laboratory of Hepato-Pancreato-Biliary Diseases, Wuhan, China.

出版信息

Aging (Albany NY). 2022 Feb 11;14(3):1473-1491. doi: 10.18632/aging.203888.

DOI:10.18632/aging.203888
PMID:35148283
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8876905/
Abstract

BACKGROUND

Epithelial-mesenchymal transition (EMT) plays a critical role in the recurrence and metastasis of hepatocellular carcinoma (HCC). Some long noncoding (lnc)RNAs are involved in this process through the regulation of EMT-related transcription factors.

METHODS

In this study, we established a novel EMT-related lncRNA signature in HCC and identified hub lncRNAs that can serve as potential therapeutic targets. Differentially expressed lncRNAs were identified by screening HCC patient data from The Cancer Genome Atlas, and a correlation analysis was performed to identify those associated with EMT. The EMT-related lncRNA signature was established by univariate, least absolute shrinkage and selection operator, and multivariate Cox regression analyses. After verifying the prognostic accuracy of the signature, its relationships to immune cell infiltration and immune checkpoint targets were explored. LINC01116 was identified as a hub lncRNA and its role in HCC was investigated and .

RESULTS

A 5-lncRNA signature was developed for HCC and its prognostic accuracy was assessed by survival, time-dependent receiver operating characteristic curve, clinical correlation, and Cox regression analyses. The correlation analysis showed that the lncRNA signature was closely related to immune cell infiltration and 10 immune checkpoint targets and also predicted the prognosis of HCC patients with high accuracy. and experiments revealed that LINC01116 stimulated cell proliferation, cell cycle progression, and tumor metastasis. We also found that LINC01116 was closely related to immune regulation.

CONCLUSIONS

These results demonstrate that LINC01116 is an immune-related oncogene that is associated with both EMT and immune regulation in HCC. Moreover, the EMT-related lncRNA signature that includes LINC01116 can guide risk stratification and clinical decision-making in HCC management.

摘要

背景

上皮-间充质转化(EMT)在肝细胞癌(HCC)的复发和转移中起着关键作用。一些长链非编码(lnc)RNA 通过调节 EMT 相关转录因子参与这一过程。

方法

本研究在 HCC 中建立了一个新的 EMT 相关 lncRNA 特征,并确定了可作为潜在治疗靶点的 hub lncRNA。通过筛选来自癌症基因组图谱的 HCC 患者数据,鉴定差异表达的 lncRNA,并进行相关性分析以鉴定与 EMT 相关的 lncRNA。通过单变量、最小绝对收缩和选择算子以及多变量 Cox 回归分析建立 EMT 相关 lncRNA 特征。验证该特征的预后准确性后,探讨其与免疫细胞浸润和免疫检查点靶标的关系。鉴定出 LINC01116 作为 hub lncRNA,并研究其在 HCC 中的作用。

结果

建立了一个用于 HCC 的 5-lncRNA 特征,并通过生存分析、时间依赖性接受者操作特征曲线、临床相关性和 Cox 回归分析评估其预后准确性。相关性分析表明,lncRNA 特征与免疫细胞浸润和 10 个免疫检查点靶标密切相关,并且可以准确预测 HCC 患者的预后。体内和体外实验表明,LINC01116 刺激细胞增殖、细胞周期进程和肿瘤转移。我们还发现 LINC01116 与免疫调节密切相关。

结论

这些结果表明,LINC01116 是一种与 HCC 中的 EMT 和免疫调节相关的免疫相关癌基因。此外,包括 LINC01116 在内的 EMT 相关 lncRNA 特征可指导 HCC 管理中的风险分层和临床决策。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d98b/8876905/f701ddb94850/aging-14-203888-g010.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d98b/8876905/bcfb66573456/aging-14-203888-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d98b/8876905/8076cd90ee62/aging-14-203888-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d98b/8876905/6b6a5269a455/aging-14-203888-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d98b/8876905/f7e7f90866a0/aging-14-203888-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d98b/8876905/4c6a742f3c3f/aging-14-203888-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d98b/8876905/1066a264886b/aging-14-203888-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d98b/8876905/019924c2d603/aging-14-203888-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d98b/8876905/499078923202/aging-14-203888-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d98b/8876905/d815735e6b0b/aging-14-203888-g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d98b/8876905/f701ddb94850/aging-14-203888-g010.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d98b/8876905/bcfb66573456/aging-14-203888-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d98b/8876905/8076cd90ee62/aging-14-203888-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d98b/8876905/6b6a5269a455/aging-14-203888-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d98b/8876905/f7e7f90866a0/aging-14-203888-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d98b/8876905/4c6a742f3c3f/aging-14-203888-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d98b/8876905/1066a264886b/aging-14-203888-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d98b/8876905/019924c2d603/aging-14-203888-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d98b/8876905/499078923202/aging-14-203888-g008.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d98b/8876905/f701ddb94850/aging-14-203888-g010.jpg

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