NR2F2 and its contribution to lymph node metastasis in oral squamous cell carcinoma

IF 4.4 2区生物学 Q2 CELL BIOLOGY

Cellular signalling Pub Date : 2025-04-20 DOI:10.1016/j.cellsig.2025.111814

Xuan-Hao Liu , Nian-Nian Zhong , Jing-Rui Yi , Guang-Rui Wang , Yao Xiao , Zheng-Rui Zhu , Qi-Wen Man , Zheng Li , Bing Liu , Lin-Lin Bu

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引用次数: 0

Abstract

Objectives

To investigate the role of cancer stem cells (CSCs) in lymph node metastasis (LNM) of oral squamous cell carcinoma (OSCC), focusing on the expression and biological significance of nuclear receptor subfamily 2 group F member 2 (NR2F2).

Methods

Single-cell RNA sequencing data from OSCC patients were analyzed using the CytoTRACE algorithm to assess stemness. Gene set scores were calculated with the irGSEA and GSVA R packages. GO and KEGG analyses identified enriched pathways. NR2F2 and CD44 expression in OSCC and lymph nodes (LNs) were validated via immunohistochemistry and immunofluorescence. NR2F2/Nr2f2 overexpression and knockdown cell lines were established, with stemness markers confirmed by Western blot. Functional assays evaluated stemness, proliferation, migration, and invasion capabilities of OSCC cells. In vivo experiments evaluated the ability of NR2F2 to promote tumor growth and metastasis. Bulk RNA sequencing and drug sensitivity analyses explored NR2F2-related mechanisms and drug responses.

Results

CSCs in OSCC were divided into five subgroups, with NR2F2 identified as the key gene in CSC4, the subgroup with the highest stemness, and found to be overexpressed in metastatic LNs. Immunohistochemistry showed NR2F2 overexpression in OSCC, associated with LNM. Immunofluorescence confirmed co-expression of NR2F2 and CD44 in metastatic OSCC and LNs. Overexpression of NR2F2 enhanced stemness, proliferation, and migration of OSCC cells. In vivo experiments showed that NR2F2 promoted the growth and LNM of OSCC. Bulk RNA sequencing revealed that NR2F2 is involved in multiple pathways and plays a role in LNM. Trametinib was identified as a sensitive drug.

Conclusion

NR2F2 is associated with the maintenance of tumor stemness and may influence LNM in OSCC by promoting tumor cell proliferation and migration.

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NR2F2 及其对口腔鳞状细胞癌淋巴结转移的影响

目的探讨肿瘤干细胞（cancer stem cells, CSCs）在口腔鳞癌（oral squamous cell carcinoma， OSCC）淋巴结转移（lymph node metastasis， LNM）中的作用，重点研究核受体亚家族2组F成员2 （NR2F2）的表达及其生物学意义。方法采用CytoTRACE算法对OSCC患者单细胞RNA测序数据进行分析。使用irGSEA和GSVA R包计算基因集评分。GO和KEGG分析发现了富集的通路。通过免疫组织化学和免疫荧光检测NR2F2和CD44在OSCC和淋巴结（LNs）中的表达。建立NR2F2/ NR2F2过表达和敲低细胞株，并通过Western blot证实其干性标记。功能分析评估OSCC细胞的干性、增殖、迁移和侵袭能力。体内实验评估了NR2F2促进肿瘤生长和转移的能力。大量RNA测序和药物敏感性分析探索nr2f2相关机制和药物反应。结果OSCC中的scscs分为5个亚组，其中NR2F2为CSC4的关键基因，是干细胞性最高的亚组，在转移性LNs中过度表达。免疫组织化学显示NR2F2在OSCC中过表达，与LNM相关。免疫荧光证实NR2F2和CD44在转移性OSCC和LNs中共表达。过表达NR2F2可增强OSCC细胞的干性、增殖和迁移能力。体内实验表明，NR2F2促进了OSCC的生长和LNM。大量RNA测序显示NR2F2参与多种途径，在LNM中发挥作用。曲美替尼被鉴定为敏感药物。结论nr2f2与肿瘤干性维持有关，可能通过促进肿瘤细胞的增殖和迁移影响OSCC的LNM。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Cellular signalling 生物-细胞生物学

CiteScore

8.40

自引率

0.00%

发文量

250

审稿时长

27 days

期刊介绍： Cellular Signalling publishes original research describing fundamental and clinical findings on the mechanisms, actions and structural components of cellular signalling systems in vitro and in vivo. Cellular Signalling aims at full length research papers defining signalling systems ranging from microorganisms to cells, tissues and higher organisms.