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PLEKHA4 knockdown induces apoptosis in melanoma cells through the MAPK and β‑catenin signaling pathways

  • Authors:
    • Yuyang Yue
    • Guangqi An
    • Shuxia Cao
    • Xiangdan Li
    • Liping Du
    • Dongyuan Xu
    • Lan Liu
  • View Affiliations / Copyright

    Affiliations: Department of Pathology, Yanbian University Hospital, Yanji, Jilin 133000, P.R. China, Department of Ophthalmology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, P.R. China, Key Laboratory of Cellular Function and Pharmacology of Jilin Province, Medical College of Yanbian University, Yanji, Jilin 133002, P.R. China, Center of Morphological Experiment, Medical College of Yanbian University, Yanji, Jilin 133002, P.R. China
    Copyright: © Yue et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 99
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    Published online on: February 18, 2025
       https://doi.org/10.3892/mmr.2025.13464
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Abstract

Malignant melanoma (MM) is a highly aggressive subtype of skin cancer characterized by a poor prognosis, particularly in the advanced stages. Despite advancements in targeted therapy and immunotherapy, the survival rates for MM remain low, underscoring the need for new therapeutic targets. Pleckstrin homology domain‑containing family A member 4 (PLEKHA4), which has regulatory functions in pivotal cellular processes, has emerged as a potential target in melanoma. The present study aimed to investigate the role of PLEKHA4 in melanoma progression, focusing on its influence on the MAPK and Wnt/β‑catenin signaling pathways. Bioinformatics analysis revealed that PLEKHA4 was upregulated in melanoma tissues, whereas PLEKHA4 knockdown in melanoma cell lines (A375 and A2058) significantly inhibited cell proliferation and migration, enhanced apoptosis and inhibited tumor growth in vivo. Mechanistic studies demonstrated that PLEKHA4 may exert its effects by modulating the MAPK signaling pathway through interactions with key proteins, including ERK, JNK and MEK. Additionally, PLEKHA4 was shown to impact apoptosis by regulating caspase‑3, COX2 and p65. Additionally, β‑catenin nuclear translocation was affected via the Wnt pathway. Moreover, PLEKHA4 knockdown reduced cMyc ubiquitination, consequently promoting its degradation. The present findings suggested that PLEKHA4 could promote melanoma cell proliferation by regulating both the MAPK and Wnt/β‑catenin pathways, thereby proposing PLEKHA4 as a promising therapeutic target for MM. Further studies are warranted to elucidate the mechanisms underlying PLEKHA4‑mediated modulation of cMyc ubiquitination.
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Copy and paste a formatted citation
Spandidos Publications style
Yue Y, An G, Cao S, Li X, Du L, Xu D and Liu L: PLEKHA4 knockdown induces apoptosis in melanoma cells through the MAPK and β‑catenin signaling pathways. Mol Med Rep 31: 99, 2025.
APA
Yue, Y., An, G., Cao, S., Li, X., Du, L., Xu, D., & Liu, L. (2025). PLEKHA4 knockdown induces apoptosis in melanoma cells through the MAPK and β‑catenin signaling pathways. Molecular Medicine Reports, 31, 99. https://doi.org/10.3892/mmr.2025.13464
MLA
Yue, Y., An, G., Cao, S., Li, X., Du, L., Xu, D., Liu, L."PLEKHA4 knockdown induces apoptosis in melanoma cells through the MAPK and β‑catenin signaling pathways". Molecular Medicine Reports 31.4 (2025): 99.
Chicago
Yue, Y., An, G., Cao, S., Li, X., Du, L., Xu, D., Liu, L."PLEKHA4 knockdown induces apoptosis in melanoma cells through the MAPK and β‑catenin signaling pathways". Molecular Medicine Reports 31, no. 4 (2025): 99. https://doi.org/10.3892/mmr.2025.13464
Copy and paste a formatted citation
x
Spandidos Publications style
Yue Y, An G, Cao S, Li X, Du L, Xu D and Liu L: PLEKHA4 knockdown induces apoptosis in melanoma cells through the MAPK and β‑catenin signaling pathways. Mol Med Rep 31: 99, 2025.
APA
Yue, Y., An, G., Cao, S., Li, X., Du, L., Xu, D., & Liu, L. (2025). PLEKHA4 knockdown induces apoptosis in melanoma cells through the MAPK and β‑catenin signaling pathways. Molecular Medicine Reports, 31, 99. https://doi.org/10.3892/mmr.2025.13464
MLA
Yue, Y., An, G., Cao, S., Li, X., Du, L., Xu, D., Liu, L."PLEKHA4 knockdown induces apoptosis in melanoma cells through the MAPK and β‑catenin signaling pathways". Molecular Medicine Reports 31.4 (2025): 99.
Chicago
Yue, Y., An, G., Cao, S., Li, X., Du, L., Xu, D., Liu, L."PLEKHA4 knockdown induces apoptosis in melanoma cells through the MAPK and β‑catenin signaling pathways". Molecular Medicine Reports 31, no. 4 (2025): 99. https://doi.org/10.3892/mmr.2025.13464
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