Open Access

Epigenetic silencing of JAM3 promotes laryngeal squamous cell carcinoma development by inhibiting the Hippo pathway

  • Authors:
    • Yue Jia
    • Jiaojiao Liu
    • Junqi Shi
    • Chunming Zhang
    • Xinfang Wang
    • Liting Zhao
    • Yichen Lou
    • Xiaoya Guan
    • Hui Huangfu
  • View Affiliations

  • Published online on: December 30, 2024     https://doi.org/10.3892/or.2024.8861
  • Article Number: 28
  • Copyright: © Jia et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Laryngeal squamous cell carcinoma (LSCC), which represents a significant proportion of head and neck squamous cell carcinoma cases, is often diagnosed at advanced stages, underscoring the urgent need for effective biomarkers and therapeutic targets. Junctional adhesion molecule 3 (JAM3) is implicated in various types of cancer; however, its role in LSCC remains unclear. Therefore, the present study aimed to investigate the epigenetic regulation and tumor‑suppressive functions and mechanisms of JAM3 in LSCC. Bioinformatics analysis and 5‑Aza‑2'‑deoxycytidine treatment, which restored JAM3 expression as confirmed by reverse transcription‑quantitative PCR and western blotting, revealed that aberrant hypermethylation of the JAM3 promoter was associated with reduced JAM3 expression and poorer clinical outcomes in patients with LSCC. In vitro experiments, including Cell Counting Kit 8, colony formation and Transwell assays, demonstrated that JAM3 overexpression inhibited LSCC cell proliferation, migration and invasion. Western blotting and immunofluorescence analysis revealed that the tumor‑suppressive function of JAM3 was mediated through activation of the Hippo pathway. By contrast, both in vitro and in vivo experiments showed that JAM3 knockdown enhanced these oncogenic behaviors by inhibiting the Hippo pathway, suggesting its critical tumor‑suppressive role. In conclusion, the results of the present study indicated that JAM3 may be epigenetically downregulated and could function as a novel tumor suppressor gene through the Hippo pathway in LSCC, offering insights into developing targeted treatments and diagnostics.
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February-2025
Volume 53 Issue 2

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Spandidos Publications style
Jia Y, Liu J, Shi J, Zhang C, Wang X, Zhao L, Lou Y, Guan X and Huangfu H: Epigenetic silencing of <em>JAM3</em> promotes laryngeal squamous cell carcinoma development by inhibiting the Hippo pathway. Oncol Rep 53: 28, 2025.
APA
Jia, Y., Liu, J., Shi, J., Zhang, C., Wang, X., Zhao, L. ... Huangfu, H. (2025). Epigenetic silencing of <em>JAM3</em> promotes laryngeal squamous cell carcinoma development by inhibiting the Hippo pathway. Oncology Reports, 53, 28. https://doi.org/10.3892/or.2024.8861
MLA
Jia, Y., Liu, J., Shi, J., Zhang, C., Wang, X., Zhao, L., Lou, Y., Guan, X., Huangfu, H."Epigenetic silencing of <em>JAM3</em> promotes laryngeal squamous cell carcinoma development by inhibiting the Hippo pathway". Oncology Reports 53.2 (2025): 28.
Chicago
Jia, Y., Liu, J., Shi, J., Zhang, C., Wang, X., Zhao, L., Lou, Y., Guan, X., Huangfu, H."Epigenetic silencing of <em>JAM3</em> promotes laryngeal squamous cell carcinoma development by inhibiting the Hippo pathway". Oncology Reports 53, no. 2 (2025): 28. https://doi.org/10.3892/or.2024.8861