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基于生物信息学的分析显示,CYTL1升高是BRAF突变型黑色素瘤的潜在治疗靶点。

Bioinformatics-based analysis reveals elevated CYTL1 as a potential therapeutic target for BRAF-mutated melanoma.

作者信息

Tao Lei, Cui Yingyue, Sun Jiarui, Cao Yu, Dai Zhen, Ge Xiaoming, Zhang Ling, Ma Run, Liu Yunyao

机构信息

Nanjing Institute for Food and Drug Control, Nanjing, China.

State Key Laboratory of Natural Medicines, School of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, Nanjing, China.

出版信息

Front Cell Dev Biol. 2023 Sep 6;11:1171047. doi: 10.3389/fcell.2023.1171047. eCollection 2023.

Abstract

Despite many recent emerging therapeutic modalities that have prolonged the survival of melanoma patients, the prognosis of melanoma remains discouraging, and further understanding of the mechanisms underlying melanoma progression is needed. Melanoma patients often have multiple genetic mutations, with BRAF mutations being the most common. In this study, public databases were exploited to explore a potential therapeutic target for BRAF-mutated melanoma. In this study, we analyzed differentially expressed genes (DEGs) in normal tissues and melanomas, Braf wild-type and Braf mutant melanomas using information from TCGA databases and the GEO database. Subsequently, we analyzed the differential expression of CYTL1 in various tumor tissues and its effect on melanoma prognosis, and resolved the mutation status of CYTL1 and its related signalling pathways. By knocking down CYTL1 in melanoma cells, the effects of CYTL1 on melanoma cell proliferation, migration and invasion were further examined by CCK8 assay, Transwell assay and cell migration assay. 24 overlapping genes were identified by analyzing DEGs common to melanoma and normal tissue, BRAF-mutated and BRAF wild-type melanoma. Among them, CYTL1 was highly expressed in melanoma, especially in BRAF-mutated melanoma, and the high expression of CYTL1 was associated with epithelial-mesenchymal transition (EMT), cell cycle, and cellular response to UV. In melanoma patients, especially BRAF-mutated melanoma patients, clinical studies showed a positive correlation between increased CYTL1 expression and shorter overall survival (OS) and disease-free survival (DFS). experiments further confirmed that the knockdown of CYTL1 significantly inhibited the migration and invasive ability of melanoma cells. CYTL1 is a valuable prognostic biomarker and a potentially effective therapeutic target in melanoma, especially BRAF-mutated melanoma.

摘要

尽管最近出现了许多延长黑色素瘤患者生存期的治疗方法,但黑色素瘤的预后仍然不容乐观,需要进一步了解黑色素瘤进展的潜在机制。黑色素瘤患者通常有多种基因突变,其中BRAF突变最为常见。在本研究中,利用公共数据库探索BRAF突变型黑色素瘤的潜在治疗靶点。在本研究中,我们使用来自TCGA数据库和GEO数据库的信息,分析了正常组织与黑色素瘤、Braf野生型和Braf突变型黑色素瘤中的差异表达基因(DEG)。随后,我们分析了CYTL1在各种肿瘤组织中的差异表达及其对黑色素瘤预后的影响,并解析了CYTL1的突变状态及其相关信号通路。通过敲低黑色素瘤细胞中的CYTL1,利用CCK8检测、Transwell检测和细胞迁移检测进一步研究了CYTL1对黑色素瘤细胞增殖、迁移和侵袭的影响。通过分析黑色素瘤与正常组织、BRAF突变型和BRAF野生型黑色素瘤共有的DEG,鉴定出24个重叠基因。其中,CYTL1在黑色素瘤中高表达,尤其是在BRAF突变型黑色素瘤中,CYTL1的高表达与上皮-间质转化(EMT)、细胞周期以及细胞对紫外线的反应有关。在黑色素瘤患者中,尤其是BRAF突变型黑色素瘤患者,临床研究表明CYTL1表达增加与总生存期(OS)和无病生存期(DFS)缩短呈正相关。实验进一步证实,敲低CYTL1可显著抑制黑色素瘤细胞的迁移和侵袭能力。CYTL1是黑色素瘤,尤其是BRAF突变型黑色素瘤中有价值的预后生物标志物和潜在有效的治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d5ee/10516578/e08a1d59d6c2/fcell-11-1171047-g001.jpg

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