Potential of CLSPN as a therapeutic target in melanoma: a key player in melanoma progression and tumor microenvironment

  • J Transl Med. 2025 Apr 24;23(1):470. doi: 10.1186/s12967-025-06455-w.
Yongyi Xie  #  1 ,  Ruoqi Wang  #  1  2 ,  Mingyuan Xu  #  1 ,  Jiashe Chen  1 ,  Wei Tan  1 ,  Yanbin Chen  1 ,  Yun Bai  1 ,  Nanhui Wu  1 ,  Fei Wu  1 ,  Xiaoxiang Xu  1 ,  Xin Ma  3  4 ,  Yeqiang Liu  5  6  7
Affiliations
  • 1. Shanghai Skin Disease Hospital, Institute of Dermatology, School of Medicine, Tongji University, Shanghai, China.
  • 2. Shanghai Skin Disease Hospital, Shanghai Skin Disease Clinical College, The Fifth Clinical Medical College, Anhui Medical University, Shanghai, 200443, China.
  • 3. Shanghai Skin Disease Hospital, Institute of Dermatology, School of Medicine, Tongji University, Shanghai, China. [email protected].
  • 4. , Baode Road 1278 street, Shanghai, 200433, China. [email protected].
  • 5. Shanghai Skin Disease Hospital, Institute of Dermatology, School of Medicine, Tongji University, Shanghai, China. [email protected].
  • 6. Shanghai Skin Disease Hospital, Shanghai Skin Disease Clinical College, The Fifth Clinical Medical College, Anhui Medical University, Shanghai, 200443, China. [email protected].
  • 7. , Baode Road 1278 street, Shanghai, 200433, China. [email protected].
  • # Contributed equally.
PMID: 40275302 DOI: 10.1186/s12967-025-06455-w
Abstract

Background: Melanoma is a highly aggressive form of skin Cancer. Despite significant advances in targeted therapies and immunotherapeutic approaches, some patients still have poor response rates, making a deeper understanding of melanoma pathogenesis essential.

Methods: The expression of Claspin (CLSPN), prognosis and immune infiltration in skin cutaneous melanoma patients were analyzed by public databases. Immunohistochemistry was used to validate. Moreover, quantitative real-time polymerase chain reaction analysis, western blot, cell counting kit-8 assay, colony formation assay, flow cytometry, animal experiments, and RNA-seq were applied to explore its biological functions and potential molecular mechanisms of CLSPN in melanoma.

Results: Our results demonstrated that abnormal CLSPN expression was correlated with poor prognosis in melanoma. Meanwhile, CLSPN may promote melanoma growth and progression in vivo and in vitro through IFI44L/JAK/STAT1 signaling. Additionally, CLSPN was associated with negative immune microenvironment in melanoma and may be related to polarization of tumor associated macrophages towards M2-type.

Conclusions: These findings suggest that CLSPN may be a promising new target for melanoma and accelerate personalized therapeutic strategies.

Keywords
CLSPN; SKCM; TAMs; Tumor immunological microenvironment.
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