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SLC7A2-CPB2 对淋巴管生成的调控作用:抑制头颈部鳞状细胞癌淋巴转移的新方法。

Regulatory Effects of SLC7A2-CPB2 on Lymphangiogenesis: A New Approach to Suppress Lymphatic Metastasis in HNSCC.

机构信息

Department of Otorhinolaryngology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.

Department of Otorhinolaryngology, The Affiliated Hospital of Guizhou Medical University, Guiyang, China.

出版信息

Cancer Med. 2024 Oct;13(19):e70273. doi: 10.1002/cam4.70273.

Abstract

BACKGROUND

Lymph node metastasis (LNM) is a critical factor affecting the outcomes of head and neck squamous cell carcinoma (HNSCC) and the main reason for treatment failure. This study was designed to examine the effects of the key genes involved in the LNM of HNSCC.

METHODS

Tissue samples (HNSCC) were examined by transcriptome sequencing, and the core genes associated with LNM were detected via bioinformatics analysis. The functions of these core genes were then validated using the TCGA biological database and their effects on the propagation, invasion, and metastasis of HNSCC cells were evaluated through cell culture experiments. Moreover, the effect of core gene expression on the LNM capability of HNSCC was confirmed via a footpad xenograft mice model.

RESULTS

In the findings, a key gene involved in the LNM of HNSCC was identified as SLC7A2. It was correlated with adverse clinical prognosis and expressed with low expression in HNSCC tissues. As shown in cell culture experiments, FaDu and SCC15 cell growth, invasion, and migration were inhibited when SLC7A2 was overexpressed. Further, cell apoptosis was stimulated, and lymphangiogenesis was suppressed through the downregulation of CPB2 expression. Animal studies demonstrated that the growth and LNM of HNSCC cells were inhibited by SLC7A2 overexpression.

CONCLUSION

It is concluded that SLC7A2 is involved in HNSCC lymphatic metastasis by controlling CPB2 function. The results are anticipated to offer new directions for the effective treatment of HNSCC.

摘要

背景

淋巴结转移(LNM)是影响头颈部鳞状细胞癌(HNSCC)结局的关键因素,也是治疗失败的主要原因。本研究旨在探讨与 HNSCC LNM 相关的关键基因的作用。

方法

通过转录组测序检测组织样本(HNSCC),并通过生物信息学分析检测与 LNM 相关的核心基因。然后使用 TCGA 生物数据库验证这些核心基因的功能,并通过细胞培养实验评估它们对 HNSCC 细胞增殖、侵袭和转移的影响。此外,通过足底异种移植小鼠模型证实核心基因表达对 HNSCC LNM 能力的影响。

结果

研究发现,SLC7A2 是与 HNSCC LNM 相关的关键基因。它与不良临床预后相关,在 HNSCC 组织中表达水平较低。在细胞培养实验中,过表达 SLC7A2 可抑制 FaDu 和 SCC15 细胞的生长、侵袭和迁移。此外,下调 CPB2 表达可刺激细胞凋亡并抑制淋巴管生成。动物研究表明,过表达 SLC7A2 可抑制 HNSCC 细胞的生长和 LNM。

结论

SLC7A2 通过控制 CPB2 功能参与 HNSCC 淋巴转移。研究结果有望为 HNSCC 的有效治疗提供新的方向。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0948/11468304/d942c318ac4c/CAM4-13-e70273-g001.jpg

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