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全面分析阐明HOXB8在头颈部鳞状细胞癌中的作用:来自多组学分析和实验验证的证据

Comprehensive analysis illustrating the role of HOXB8 in head and neck squamous cell carcinoma: evidence from multi-omics analysis and experiments validation.

作者信息

Zhang Jun-Wei, Gao Xi-Lin, Wang Jing, Fan Xue-Li, Liang Qi-Wei

机构信息

Longgang Center Hospital, the ninth people's hospital of shenzhen, Shenzhen, China.

出版信息

BMC Cancer. 2025 Apr 30;25(1):804. doi: 10.1186/s12885-025-14205-w.

DOI:10.1186/s12885-025-14205-w
PMID:40307753
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12042558/
Abstract

BACKGROUND

HOXB8 is implicated in various cancers. However, the effect pattern of HOXB8 in head and neck squamous cell carcinoma (HNSCC) remains unclear.

METHODS

Open-access transcriptional profiles, clinical information, and mutational data were downloaded from the Cancer Genome Atlas database. R software was used for all analysis based on public data through specific R packages. Western blot and real-time quantitative PCR was used to detect the protein and RNA level of HOXB8, respectively. In vivo and in vitro experiments were conducted to explore the effect of HOXB8 on HNSCC cells.

RESULTS

Here, we discovered that HOXB8 was upregulated in HNSCC tissue and associated with worse clinical outcomes (clinical stage and prognosis). Results indicated that HOXB8 was primarily distributed in the nucleoplasm. Results of cell lines indicated that HOXB8 is upregulated in HNSCC cells. Further experiments, both in vitro and in vivo, revealed that the suppression of HOXB8 can markedly curb the proliferation, invasion, and migration capabilities of HNSCC cells. Results of biological enrichment and western blot indicated that HOXB8 can regulate the PI3K/AKT/mTOR and EMT pathways. It also came to our attention that HOXB8 could modulate the tumor microenvironment in HNSCC. We observed that patients with high HOXB8 expression had lower infiltration levels of CD8 + T cells but higher infiltration levels of M2 macrophages. Finally, we developed a prognostic model based on molecules derived from HOXB8 (ADD2, SYT1, PXYLP1, MRPL33).

CONCLUSIONS

Our study contributes to the existing knowledge on HOXB8 in HNSCC, which may inform future research directions.

摘要

背景

HOXB8与多种癌症有关。然而,HOXB8在头颈部鳞状细胞癌(HNSCC)中的作用模式仍不清楚。

方法

从癌症基因组图谱数据库下载开放获取的转录谱、临床信息和突变数据。基于公共数据,使用R软件通过特定的R包进行所有分析。分别使用蛋白质免疫印迹法和实时定量PCR检测HOXB8的蛋白质和RNA水平。进行体内和体外实验以探究HOXB8对HNSCC细胞的影响。

结果

在此,我们发现HOXB8在HNSCC组织中上调,并与较差的临床结果(临床分期和预后)相关。结果表明HOXB8主要分布在核质中。细胞系结果表明HOXB8在HNSCC细胞中上调。进一步的体内和体外实验表明,抑制HOXB8可显著抑制HNSCC细胞的增殖、侵袭和迁移能力。生物富集和蛋白质免疫印迹结果表明HOXB8可调节PI3K/AKT/mTOR和EMT信号通路。我们还注意到HOXB8可调节HNSCC中的肿瘤微环境。我们观察到HOXB8高表达的患者CD8 + T细胞浸润水平较低,但M2巨噬细胞浸润水平较高。最后,我们基于源自HOXB8的分子(ADD2、SYT1、PXYLP1、MRPL33)建立了一个预后模型。

结论

我们的研究为现有关于HOXB8在HNSCC中的知识做出了贡献,这可能为未来的研究方向提供参考。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2dc3/12042558/4558c68ee80c/12885_2025_14205_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2dc3/12042558/fa74a8453354/12885_2025_14205_Fig1_HTML.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2dc3/12042558/05c1d38c8274/12885_2025_14205_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2dc3/12042558/8bdda387a010/12885_2025_14205_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2dc3/12042558/70d373517537/12885_2025_14205_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2dc3/12042558/4558c68ee80c/12885_2025_14205_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2dc3/12042558/fa74a8453354/12885_2025_14205_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2dc3/12042558/bd54a6534795/12885_2025_14205_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2dc3/12042558/bfbd3f37358b/12885_2025_14205_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2dc3/12042558/05c1d38c8274/12885_2025_14205_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2dc3/12042558/8bdda387a010/12885_2025_14205_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2dc3/12042558/70d373517537/12885_2025_14205_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2dc3/12042558/4558c68ee80c/12885_2025_14205_Fig7_HTML.jpg

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本文引用的文献

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Int J Mol Sci. 2022 Dec 12;23(24):15749. doi: 10.3390/ijms232415749.
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Exosomal lncRNA HOTAIR induce macrophages to M2 polarization via PI3K/ p-AKT /AKT pathway and promote EMT and metastasis in laryngeal squamous cell carcinoma.外泌体长链非编码 RNA HOTAIR 通过 PI3K/ p-AKT / AKT 通路诱导巨噬细胞向 M2 极化,促进喉鳞状细胞癌的 EMT 和转移。
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Claudin-1 mediates progression by regulating EMT through AMPK/TGF-β signaling in head and neck squamous cell carcinoma.
Claudin-1 通过调节 AMPK/TGF-β 信号通路在头颈部鳞状细胞癌中促进 EMT 进展。
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CD8 T-cell exhaustion in the tumor microenvironment of head and neck squamous cell carcinoma determines poor prognosis.头颈部鳞状细胞癌肿瘤微环境中的CD8 T细胞耗竭决定了预后不良。
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