BAP1 deletion abrogates growth and metastasis of murine cutaneous melanoma.

Abstract

Although germline mutations in BRCA-associated protein-1 (BAP1) predispose to cutaneous melanoma (CM), BAP1 is rarely mutated in primary CM outside the familial context. The role of BAP1 in the pathogenesis of CM remains obscure. Here, we discovered an unexpected role of BAP1 in suppressing CM growth and metastasis. BAP1 deletion by CRISPR-Cas9 system severely compromises colony-forming capability of murine CM cell line B16-F10 and human CM cell lines, SK-MEL-28 and A375. Furthermore, BAP1 loss abrogates tumor growth and lung metastasis in murine syngeneic tumor models. Deletion of BAP1 in B16-F10 cells leads to preferential downregulation of genes accompanied with increased H2A ubiquitination at lysine 119. Transcriptomic characterization of BAP1 deletion reveals multiple deregulated cellular functions including extracellular matrix-receptor interaction and MAPK signaling pathway which may contribute to BAP1's effect on metastasis and proliferation. Our findings indicate that BAP1 could be a potential therapeutic target for CM.

• Authors: Xin Luo, Yuyan Xu, Yilei Li, Guiming Zhang, Sisi Huang, Xiaolian Liu, Zhonglu Ren, Shuwen Liu, Le Yu
• Journal: Melanoma research (Melanoma Res) Vol. 31 Issue 2 Pg. 119-129 (04 01 2021) ISSN: 1473-5636 [Electronic] England
• PMID: 33347048 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2020 The Author(s). Published by Wolters Kluwer Health, Inc.

Chemical References

• BAP1 protein, mouse
• Tumor Suppressor Proteins
• Ubiquitin Thiolesterase

Topics

• Animals
• Humans
• Melanoma (genetics)
• Mice
• Mice, Nude
• Neoplasm Metastasis
• Skin Neoplasms (genetics)
• Transfection
• Tumor Suppressor Proteins (metabolism)
• Ubiquitin Thiolesterase (metabolism)