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Abstract：
BACKGROUND: Anaplastic thyroid carcinoma (ATC) is an extremely aggressive solid tumor with no effective treatment at present. Because of the rapid growth and aggressiveness, nearly all patients die within six months after developing ATC. Hence, more research regarding novel therapeutic targets for ATC is urgently needed.
METHODS: Single-cell RNA sequencing data and microarray data of ATC were retrieved from the Gene Expression Omnibus (GEO) database. Cell clustering was performed using the Seurat package. Then, differential expression and functional enrichment analyses were performed. Gene set enrichment analysis (GSEA) was further used to investigate the functional enrichment of lysyl oxidase (LOX) and bone morphogenetic protein-1 (BMP1). The expression levels of LOX and BMP1 were measured using quantitative real-time PCR and Western blot. LOX and BMP1 were knocked down using si-RNAs. Cell proliferation was evaluated by the CCK-8 and clone formation assays. Cell migration and invasion were assessed by the wound healing assay and Transwell assay, respectively.
RESULTS: LOX was upregulated at the single-cell level, as well as in ATC tissues and cell lines. LOX knockdown significantly inhibited ATC cell proliferation. Furthermore, the migration and invasion of ATC cells were remarkably inhibited after LOX inhibition. In addition, BMP1 regulated LOX expression in 8505C cells, while BMP1 overexpression restored the LOX activity blocked by the LOX inhibitor BAPN. BMP1 could also induce the cell proliferation and metastasis of ATC.
CONCLUSIONS: LOX/BMP1 mediates the malignant progression of ATC, highlighting the potential application of LOX/BMP1 in the treatment of ATC. This study provides new insights for efficient therapeutic agents based on the LOX/BMP1 axis.
METHODS: Single-cell RNA sequencing data and microarray data of ATC were retrieved from the Gene Expression Omnibus (GEO) database. Cell clustering was performed using the Seurat package. Then, differential expression and functional enrichment analyses were performed. Gene set enrichment analysis (GSEA) was further used to investigate the functional enrichment of lysyl oxidase (LOX) and bone morphogenetic protein-1 (BMP1). The expression levels of LOX and BMP1 were measured using quantitative real-time PCR and Western blot. LOX and BMP1 were knocked down using si-RNAs. Cell proliferation was evaluated by the CCK-8 and clone formation assays. Cell migration and invasion were assessed by the wound healing assay and Transwell assay, respectively.
RESULTS: LOX was upregulated at the single-cell level, as well as in ATC tissues and cell lines. LOX knockdown significantly inhibited ATC cell proliferation. Furthermore, the migration and invasion of ATC cells were remarkably inhibited after LOX inhibition. In addition, BMP1 regulated LOX expression in 8505C cells, while BMP1 overexpression restored the LOX activity blocked by the LOX inhibitor BAPN. BMP1 could also induce the cell proliferation and metastasis of ATC.
CONCLUSIONS: LOX/BMP1 mediates the malignant progression of ATC, highlighting the potential application of LOX/BMP1 in the treatment of ATC. This study provides new insights for efficient therapeutic agents based on the LOX/BMP1 axis.
摘要：
背景：间变性甲状腺癌（ATC）是一种侵袭性极强的实体瘤，目前尚无有效的治疗方法。由于快速增长和侵略性，几乎所有患者在发生ATC后6个月内死亡。因此，迫切需要更多关于ATC新治疗靶点的研究.
方法：从基因表达综合（GEO）数据库中检索ATC的单细胞RNA测序数据和微阵列数据。使用Seurat包进行细胞聚类。然后，进行差异表达和功能富集分析。进一步使用基因集富集分析（GSEA）来研究赖氨酰氧化酶（LOX）和骨形态发生蛋白-1（BMP1）的功能富集。使用定量实时PCR和Western印迹测量LOX和BMP1的表达水平。使用si-RNA敲低LOX和BMP1。通过CCK-8和克隆形成测定评价细胞增殖。通过伤口愈合试验和Transwell试验评估细胞迁移和侵袭,分别。
结果：LOX在单细胞水平上调，以及ATC组织和细胞系。LOX敲低显著抑制ATC细胞增殖。此外，LOX抑制后ATC细胞的迁移和侵袭能力受到显著抑制。此外,BMP1调控8505C细胞中LOX的表达，而BMP1过表达恢复了LOX抑制剂BAPN阻断的LOX活性。BMP1还可以引诱ATC的细胞增殖和转移。
结论：LOX/BMP1介导ATC的恶性进展，强调LOX/BMP1在ATC治疗中的潜在应用。这项研究为基于LOX/BMP1轴的有效治疗剂提供了新的见解。
方法：从基因表达综合（GEO）数据库中检索ATC的单细胞RNA测序数据和微阵列数据。使用Seurat包进行细胞聚类。然后，进行差异表达和功能富集分析。进一步使用基因集富集分析（GSEA）来研究赖氨酰氧化酶（LOX）和骨形态发生蛋白-1（BMP1）的功能富集。使用定量实时PCR和Western印迹测量LOX和BMP1的表达水平。使用si-RNA敲低LOX和BMP1。通过CCK-8和克隆形成测定评价细胞增殖。通过伤口愈合试验和Transwell试验评估细胞迁移和侵袭,分别。
结果：LOX在单细胞水平上调，以及ATC组织和细胞系。LOX敲低显著抑制ATC细胞增殖。此外，LOX抑制后ATC细胞的迁移和侵袭能力受到显著抑制。此外,BMP1调控8505C细胞中LOX的表达，而BMP1过表达恢复了LOX抑制剂BAPN阻断的LOX活性。BMP1还可以引诱ATC的细胞增殖和转移。
结论：LOX/BMP1介导ATC的恶性进展，强调LOX/BMP1在ATC治疗中的潜在应用。这项研究为基于LOX/BMP1轴的有效治疗剂提供了新的见解。
