Department of Oral Bioscience, Tokushima University Graduate School of Biomedical Sciences, Tokushima, Japan.
Sci Rep. 2024 Mar 21;14(1):6767. doi: 10.1038/s41598-024-57478-0.
Head and neck squamous cell carcinoma (HNSCC) is a significant healthcare burden globally. Previous research using single-cell transcriptome analysis identified TGFBI as a crucial marker for the partial-epithelial-mesenchymal transition (partial-EMT) program. However, the precise role of TGFBI in HNSCC progression remains unclear. Therefore, our study aimed to clarify the impact of TGFBI on the malignant behavior of HNSCC cells. Through RNA-sequencing data from the TCGA database, we validated that increased TGFBI expression correlates with a higher occurrence of lymph node metastasis and unfavorable prognosis in HNSCC cases. Functional experiments demonstrated that TGFBI overexpression enhances the ability of sphere formation, indicating stem-cell-like properties. Conversely, TGFBI depletion reduces sphere formation and suppresses the expression of cancer stem cell (CSC) markers. RNA-sequencing analysis of TGFBI-overexpressing and control HNSCC cells revealed TAGLN as a downstream effector mediating TGFBI-induced sphere formation. Remarkably, TAGLN depletion abolished TGFBI-induced sphere formation, while its overexpression rescued the suppressed sphere formation caused by TGFBI depletion. Moreover, elevated TAGLN expression showed correlations with the expression of TGFBI and partial-EMT-related genes in HNSCC cases. In conclusion, our findings suggest that TGFBI may promote CSC properties through the upregulation of TAGLN. These novel insights shed light on the involvement of the TGFBI-TAGLN axis in HNSCC progression and hold implications for the development of targeted therapies.
头颈部鳞状细胞癌（HNSCC）是全球范围内重大的医疗保健负担。之前使用单细胞转录组分析的研究发现，TGFBI 是部分上皮-间充质转化（partial-EMT）程序的关键标志物。然而，TGFBI 在 HNSCC 进展中的确切作用仍不清楚。因此，我们的研究旨在阐明 TGFBI 对头颈部鳞状细胞癌细胞恶性行为的影响。通过 TCGA 数据库的 RNA 测序数据，我们验证了 TGFBI 表达增加与 HNSCC 病例中淋巴结转移发生率更高和预后不良相关。功能实验表明，TGFBI 过表达增强了球体形成的能力，表明具有干细胞样特性。相反，TGFBI 耗竭减少了球体形成并抑制了癌症干细胞（CSC）标志物的表达。TGFBI 过表达和对照 HNSCC 细胞的 RNA 测序分析揭示 TAGLN 是介导 TGFBI 诱导的球体形成的下游效应因子。值得注意的是，TAGLN 耗竭消除了 TGFBI 诱导的球体形成，而其过表达挽救了 TGFBI 耗竭引起的球体形成抑制。此外，升高的 TAGLN 表达与 HNSCC 病例中 TGFBI 和部分 EMT 相关基因的表达相关。总之，我们的研究结果表明，TGFBI 可能通过上调 TAGLN 促进 CSC 特性。这些新的见解揭示了 TGFBI-TAGLN 轴在 HNSCC 进展中的参与，并对靶向治疗的发展具有意义。
