NPTX2 Promotes Epithelial-Mesenchymal Transition in Cutaneous Squamous Cell Carcinoma through METTL3-Mediated N6-Methyladenosine Methylation of SNAIL.

Abstract

Cutaneous squamous cell carcinoma (cSCC) is the second most common type of skin cancer. NPTX2, a member of the neuronal pentraxin family, is reported to play inconsistent roles in different cancers. The role and mechanism of NPTX2 in cSCC remain unclear. In this study, we found that NPTX2 was overexpressed in both skin lesions and cell lines of cSCC. In vitro studies showed that NPTX2 facilitated cell proliferation, migration, invasion, colony formation, and epithelial‒mesenchymal translation in A431 and SCL-1 cells. NPTX2 interacted with METTL3, increased METTL3 expression, and improved N6-methyladenosine modification in cSCC cell lines. Mechanistically, NPTX2 facilitated epithelial‒mesenchymal translation by promoting METTL3-mediated N6-methyladenosine of SNAIL. METTL3 knockdown and N6-methyladenosine inhibition reversed the impacts of NPTX2 overexpression on cSCC cells. In vivo studies verified the role of NPTX2 as an oncogene in cSCC. Therefore, NPTX2 may be a potential therapeutic target for cSCC.

• Authors: Tong Kang, Cheng Zhang, Hao Lei, Ruiting Luo, Meng Liu, Shengbang Wang, Xiu Zhang, Qiqi Duan, Shengxiang Xiao, Yan Zheng
• Journal: The Journal of investigative dermatology (J Invest Dermatol) Vol. 143 Issue 6 Pg. 977-988.e2 (06 2023) ISSN: 1523-1747 [Electronic] United States
• PMID: 36638907 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.

Chemical References

• METTL3 protein, human
• Methyltransferases

Topics

• Humans
• Methylation
• Carcinoma, Squamous Cell (genetics, pathology)
• Epithelial-Mesenchymal Transition (genetics)
• Skin Neoplasms (genetics, pathology)
• Cell Line, Tumor
• Methyltransferases (genetics)