Transcriptome Analysis of Large to Giant Congenital Melanocytic Nevus Reveals Cell Cycle Arrest and Immune Evasion: Identifying Potential Targets for Treatment. (6th December 2021)

• Record Type: Journal Article
• Authors: Wei, Boxuan; Gu, Jieyu; Duan, Ran; Gao, Bowen; Wu, Min; Zhou, Shengliang; Huang, Xiaolu; Xie, Feng
• Other Names: Zhang Zhi Gang Academic Editor.
• Is Part Of: Journal of immunology research. Volume 2021(2021)
• Publication Date: 2021-12-06
• Subjects: Immunology -- Periodicals; Immunology -- Research -- Periodicals; 616.07905
• DOI: 10.1155/2021/8512200
• Languages: English
• ISSNs: 2314-8861

Abstract

Abstract : Large to giant congenital melanocytic nevus (lgCMN) is a benign cutaneous tumor that develops during embryogenesis. A large number of lgCMN patients are ineligible for surgical treatment; hence, there is an urgent need to develop pharmacological treatments. Clinically, tumorigenesis and progression essentially halt after birth, resulting in the homeostasis of growth arrest and survival. Numerous studies have employed whole-genome or whole-exome sequencing to clarify the etiology of lgCMN; however, transcriptome sequencing of lgCMN is still lacking. Through comprehensive transcriptome analysis, this study elucidated the ongoing regulation and homeostasis of lgCMN and identified potential targets for treatment. Transcriptome sequencing, identification of differentially expressed genes and hub genes, protein–protein network construction, functional enrichment, pathway analysis, and gene annotations were performed in this study. Immunohistochemistry, real-time quantitative PCR, immunocytofluorescence, and cell cycle assays were employed for further validation. The results revealed several intriguing phenomena in lgCMN, including P16 -induced cell cycle arrest, antiapoptotic activity, and immune evasion caused by malfunction of tumor antigen processing. The arrested cell cycle in lgCMN is consistent with its phenotype and rare malignant transformation. Antiapoptotic activity and immune evasion might explain how such heterogeneous cells have avoided elimination. Major histocompatibility complex (MHC) class I-mediated tumor antigen processing was the hub pathway that was significantly downregulated in lgCMN, and ITCH, FBXW7, HECW2, and WWP1 were identified as candidate hub genes. In conclusion, our research provides new perspectives for immunotherapy and targeted therapy.