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ELOVL6 通过激活 WNT/β-连环蛋白通路促进头颈部鳞状细胞癌的进展。

ELOVL6 promotes the progression of head and neck squamous cell carcinoma via activating WNT/β-catenin pathway.

机构信息

Department of Otolaryngology, The First Affiliated Hospital of Jinzhou Medical University, Jinzhou, China.

Department of Radiology, Beijing Tongren Hospital, Capital Medical University, Beijing, China.

出版信息

Mol Carcinog. 2024 Jun;63(6):1079-1091. doi: 10.1002/mc.23710. Epub 2024 Mar 1.

Abstract

This study was to explore the role of ELOVL6 in the development of head and neck squamous cell carcinoma (HNSCC). Considering its previously identified oncogenic role in hepatocellular carcinoma. ELOVL6 gene expression, clinicopathological analysis, enrichment analysis, and immune infiltration analysis were based on the data from Gene Expression Omnibus and The Cancer Genome Atlas, with additional bioinformatics analyses performed. Human HNSCC tissue microarray and cell lines were used. The expression of ELOVL6 in HNSCC was detected by quantitative polymerase chain reaction, immunohistochemistry assay, and western blot analysis. The proliferation ability of HNSCC cells, invasion, and apoptosis were evaluated using cell counting kit-8 method, Transwell assay, and flow cytometry, respectively. Based on the data derived from the cancer databases and our HNSCC cell and tissue studies, we found that ELOVL6 was overexpressed in HNSCC. Moreover, ELOVL6 expression level had a positive correlation with clinicopathology of HNSCC. Gene set enrichment analysis showed that ELOVL6 affected the occurrence of HNSCC through WNT signaling pathway. Functional experiments demonstrated that ELOVL6 knockdown inhibited the proliferation and invasion of HNSCC cells while promoting apoptosis. Additionally, compound 3f, an agonist of WNT/β-catenin signaling pathway, enhances the effect of ELOVL6 on the progression of HNSCC cells. ELOVL6 is upregulated in HNSCC and promotes the development of HNSCC cells by inducing WNT/β-catenin signaling pathway. ELOVL6 stands a potential target for the treatment of HNSCC and a prognosis indicator of human HNSCC.

摘要

本研究旨在探讨 ELOVL6 在头颈部鳞状细胞癌(HNSCC)发展中的作用。考虑到其先前在肝细胞癌中被鉴定为致癌基因。基于基因表达综合数据库和癌症基因组图谱的数据,进行了 ELOVL6 基因表达、临床病理分析、富集分析和免疫浸润分析,并进行了额外的生物信息学分析。使用人 HNSCC 组织微阵列和细胞系。通过定量聚合酶链反应、免疫组织化学测定和 Western blot 分析检测 HNSCC 中 ELOVL6 的表达。使用细胞计数试剂盒-8 法、Transwell 测定和流式细胞术分别评估 HNSCC 细胞的增殖能力、侵袭和凋亡。基于癌症数据库和我们的 HNSCC 细胞和组织研究的数据,我们发现 ELOVL6 在 HNSCC 中过表达。此外,ELOVL6 表达水平与 HNSCC 的临床病理具有正相关性。基因集富集分析表明,ELOVL6 通过 WNT 信号通路影响 HNSCC 的发生。功能实验表明,ELOVL6 敲低抑制 HNSCC 细胞的增殖和侵袭,同时促进凋亡。此外,WNT/β-catenin 信号通路激动剂化合物 3f 增强了 ELOVL6 对 HNSCC 细胞进展的影响。ELOVL6 在 HNSCC 中上调,并通过诱导 WNT/β-catenin 信号通路促进 HNSCC 细胞的发展。ELOVL6 可能成为治疗 HNSCC 的潜在靶点和人类 HNSCC 的预后指标。

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