Transcriptome Analysis of Large to Giant Congenital Melanocytic Nevus Reveals Cell Cycle Arrest and Immune Evasion: Identifying Potential Targets for Treatment.
Transcriptome Analysis of Large to Giant Congenital Melanocytic Nevus Reveals Cell Cycle Arrest and Immune Evasion: Identifying Potential Targets for Treatment.
复制标题
大到巨大先天性黑素细胞痣的转录组分析揭示细胞周期停滞和免疫逃避：确定潜在的治疗靶点
DOI：
10.1155/2021/8512200
复制
发表时间：
2021
影响因子：
4.1
通讯作者：
Xie F
中科院分区：
文献类型：
--
作者：
Wei B;Gu J;Duan R;Gao B;Wu M;Zhou S;Huang X;Xie F
先天性黑色素细胞痣（lgCMN）是一种在胚胎发育过程中发生的良性皮肤肿瘤。大量lgCMN患者不适合手术治疗;因此，迫切需要开发药物治疗。临床上，肿瘤发生和进展在出生后基本停止，导致生长停滞和存活的稳态。许多研究已经采用全基因组或全外显子组测序来阐明IgCMN的病因;然而，仍然缺乏IgCMN的转录组测序。通过全面的转录组分析，本研究阐明了lgCMN的持续调节和稳态，并确定了潜在的治疗靶点。本研究主要包括转录组测序、差异表达基因和枢纽基因的鉴定、蛋白质-蛋白质网络构建、功能富集、通路分析和基因注释等。采用免疫组化、实时定量PCR、免疫细胞荧光和细胞周期分析进行进一步验证。结果揭示了lgCMN中几个有趣的现象，包括P16诱导的细胞周期停滞，抗凋亡活性，以及肿瘤抗原处理功能障碍引起的免疫逃避。lgCMN中细胞周期停滞与其表型和罕见恶性转化一致。抗凋亡活性和免疫逃避可能解释了这些异质细胞如何避免被清除。主要组织相容性复合体（MHC）I类介导的肿瘤抗原加工是在IgCMN中显著下调的枢纽途径，ITCH、FBXW 7、HECW 2和WWP 1被鉴定为候选枢纽基因。总之，我们的研究为免疫治疗和靶向治疗提供了新的视角。
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.
登录
查看更多内容
影响因子：
28.2
作者：
Gstalder C;Liu D;Miao D;Lutterbach B;DeVine AL;Lin C;Shettigar M;Pancholi P;Buchbinder EI;Carter SL;Manos MP;Rojas-Rudilla V;Brennick R;Gjini E;Chen PH;Lako A;Rodig S;Yoon CH;Freeman GJ;Barbie DA;Hodi FS;Miles W;Van Allen EM;Haq R
通讯作者：
Haq R
影响因子：
6.5
作者：
Martins da Silva, Vanessa;Martinez-Barrios, Estefania;Malvehy, Josep
通讯作者：
Malvehy, Josep
影响因子：
13.8
作者：
Ibrahimi, Omar A.;Alikhan, Ali;Eisen, Daniel B.
通讯作者：
Eisen, Daniel B.
影响因子：
3
作者：
Bader, GD;Hogue, CW
通讯作者：
Hogue, CW
影响因子：
6.5
作者：
Dessars, Barbara;De Raeve, Linda E.;Heimann, Pierre
通讯作者：
Heimann, Pierre