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鉴定lncRNA-mRNA调控模块以探索黑色素瘤的发病机制和预后

Identification of lncRNA-mRNA Regulatory Module to Explore the Pathogenesis and Prognosis of Melanoma.

作者信息

Zhang Jiaqi, Liu Hui, Zhang Wenhao, Li Yinfang, Fan Zhigang, Jiang Hua, Luo Judong

机构信息

Department of Radiotherapy, The Affiliated Changzhou No. 2 People's Hospital of Nanjing Medical University, Changzhou, China.

Department of Dermatology, Graduate School of Dalian Medical University, Dalian, China.

出版信息

Front Cell Dev Biol. 2020 Dec 17;8:615671. doi: 10.3389/fcell.2020.615671. eCollection 2020.

Abstract

Skin cutaneous melanoma (SKCM) is an aggressive form of skin cancer that results in high mortality rate worldwide. It is vital to discover effective prognostic biomarkers and therapeutic targets for the treatment of melanoma. Long non-coding RNA (lncRNA) has been verified to play an essential role in the regulation of gene expression in diseases and tumors. Therefore, it is significant to explore the function of lncRNAs in the development and progression of SKCM. In this paper, a set of differentially expressed lncRNAs (DElncRNAs) and mRNAs (DEmRNAs) were first screened out using 471 cutaneous melanoma samples and 813 normal skin samples. Gene Ontology and KEGG pathway enrichment analysis were performed to obtain the significant function annotations and pathways of DEmRNAs. We also ran survival analysis on both DElncRNAs and DEmRNAs to identify prognostic-related lncRNAs and mRNAs. Next, a set of hub genes derived from protein-protein interaction (PPI) network analysis and lncRNA target genes screened from starbase-ENCORI database were integrated to construct a lncRNA-mRNA regulatory module, which includes 6 lncRNAs 4 target mRNAs. We further checked the capacity of these lncRNA and mRNA in the diagnosis of melanoma, and found that single lncRNA can effectively distinguish tumor and normal tissue. Moreover, we ran CMap analysis to select a list of small molecule drugs for SKCM, such as EGFR inhibitor AG-490, growth factor receptor inhibitor GW-441756 and apoptosis stimulant betulinic-acid, which have shown therapeutic effect in the treatment of melanoma.

摘要

皮肤黑色素瘤(SKCM)是一种侵袭性皮肤癌,在全球范围内导致高死亡率。发现有效的预后生物标志物和治疗靶点对于黑色素瘤的治疗至关重要。长链非编码RNA(lncRNA)已被证实在疾病和肿瘤的基因表达调控中起重要作用。因此,探索lncRNAs在SKCM发生发展中的功能具有重要意义。本文首先利用471例皮肤黑色素瘤样本和813例正常皮肤样本筛选出一组差异表达的lncRNAs(DElncRNAs)和mRNA(DEmRNAs)。进行基因本体论和KEGG通路富集分析以获得DEmRNAs的重要功能注释和通路。我们还对DElncRNAs和DEmRNAs进行了生存分析,以鉴定与预后相关的lncRNAs和mRNAs。接下来,整合了一组来自蛋白质-蛋白质相互作用(PPI)网络分析的枢纽基因和从starbase-ENCORI数据库筛选的lncRNA靶基因,构建了一个lncRNA-mRNA调控模块,其中包括6个lncRNAs和4个靶mRNA。我们进一步检查了这些lncRNA和mRNA在黑色素瘤诊断中的能力,发现单个lncRNA可以有效区分肿瘤组织和正常组织。此外,我们进行了CMap分析,以选择一系列用于SKCM的小分子药物,如表皮生长因子受体(EGFR)抑制剂AG-490、生长因子受体抑制剂GW-441756和凋亡刺激剂桦木酸,这些药物在黑色素瘤治疗中已显示出治疗效果。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b528/7773644/9a92333b51f4/fcell-08-615671-g0001.jpg

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