BAP1 deletion abrogates growth and metastasis of murine cutaneous melanoma

Xin Luo1,2, Yuyan Xu1,2, Yilei Li2

  • 1School of Pharmaceutical Sciences, Southern Medical University.

Melanoma Research
|December 21, 2020
PubMed

Insights

BRCA-associated protein-1 (BAP1) unexpectedly suppresses cutaneous melanoma (CM) growth and metastasis. Loss of BAP1 impairs tumor formation and spread, suggesting BAP1 as a potential therapeutic target for CM.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Germline mutations in BRCA-associated protein-1 (BAP1) are linked to hereditary cutaneous melanoma (CM).
  • The specific role of BAP1 in the development of primary CM, particularly in non-familial cases, is not well understood.

Purpose of the Study:

  • To investigate the function of BAP1 in the pathogenesis of cutaneous melanoma.
  • To determine if BAP1 plays a role in suppressing CM growth and metastasis.

Main Methods:

  • CRISPR-Cas9 gene editing was used to delete BAP1 in murine (B16-F10) and human (SK-MEL-28, A375) CM cell lines.
  • Tumor growth and lung metastasis were assessed in murine syngeneic models following BAP1 deletion.
  • Transcriptomic analysis and H2A ubiquitination assays were performed to understand the molecular mechanisms.

Main Results:

  • BAP1 deletion significantly reduced the colony-forming ability of CM cell lines.
  • Loss of BAP1 abrogated tumor growth and lung metastasis in vivo.
  • BAP1 deletion led to downregulation of specific genes, increased H2A ubiquitination at lysine 119, and deregulation of pathways like extracellular matrix-receptor interaction and MAPK signaling.

Conclusions:

  • BAP1 acts as a suppressor of cutaneous melanoma growth and metastasis.
  • The findings highlight BAP1 as a potential therapeutic target for CM treatment.

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