Department of Oral and Maxillofacial Surgery, Affiliated Stomatology Hospital of Kunming Medical University, No. 1088 Mid Hai Yuan Road. Gaoxin District, Kunming, Yunnan, 650106, China.
Yunnan Key Laboratory of Stomatology, Kunming, Yunnan, China.
BMC Oral Health. 2024 Nov 21;24(1):1421. doi: 10.1186/s12903-024-05003-0.
This study aims to explore the regulatory mechanisms of Wnt signaling in the invasion and recurrence of ameloblastoma (AM) to provide a new theoretical basis for its treatment.
Bulk RNA sequencing was employed to analyze samples from AM patients, and identify differentially expressed genes. Subsequently, bioinformatics methods such as Weighted Gene Co-Expression Network Analysis (WGCNA), DESeq2, and KEGG enrichment analysis were utilized to construct gene co-expression networks and identify pathways associated with invasion and recurrence. Furthermore, in vitro experiments, including Cell Counting Kit-8 (CCK-8), Wound healing assays, Western blotting, and qPCR were conducted to validate the effects of Wnt signaling on AM biological functions and the expression of related genes and proteins.
Bioinformatics analysis revealed significant activation of the Wnt signaling pathway during AM invasion and recurrence, and differential gene analysis identified specific gene expression patterns associated with the Wnt signaling pathway. In vitro experiments further demonstrated that the standard Wnt/β-catenin pathway activator, Laduviglusib significantly activated Wnt signaling, leading to a marked increase in the mRNA and protein expression levels of TCF7, β-catenin, WNT2B, and LEF1, thereby enhancing the proliferation and migration capabilities of AM cells.
This study reveals the critical role of aberrant Wnt signaling activation in AM proliferation and migration, identifying it as a key driver of AM invasion and recurrence. The findings provide new insights into the mechanisms underlying AM invasion and recurrence, laying the foundation for developing novel therapeutic strategies.
本研究旨在探讨 Wnt 信号通路在成釉细胞瘤（AM）侵袭和复发中的调控机制，为其治疗提供新的理论依据。
采用 bulk RNA 测序分析 AM 患者样本，筛选差异表达基因。然后，运用加权基因共表达网络分析（WGCNA）、DESeq2 和 KEGG 富集分析等生物信息学方法构建基因共表达网络，并识别与侵袭和复发相关的通路。此外，还进行了体外实验，包括细胞计数试剂盒（CCK-8）、划痕愈合实验、Western blot 和 qPCR，以验证 Wnt 信号通路对 AM 生物学功能以及相关基因和蛋白表达的影响。
生物信息学分析显示，Wnt 信号通路在 AM 侵袭和复发过程中显著激活，差异基因分析鉴定出与 Wnt 信号通路相关的特定基因表达模式。体外实验进一步表明，标准 Wnt/β-catenin 通路激活剂 Laduviglusib 可显著激活 Wnt 信号通路，导致 TCF7、β-catenin、WNT2B 和 LEF1 的 mRNA 和蛋白表达水平显著增加，从而增强 AM 细胞的增殖和迁移能力。
本研究揭示了异常 Wnt 信号激活在 AM 增殖和迁移中的关键作用，确定其为 AM 侵袭和复发的关键驱动因素。研究结果为探讨 AM 侵袭和复发的机制提供了新的视角，为开发新的治疗策略奠定了基础。
