成釉细胞瘤患者lncRNA-mRNA共表达网络分析及作用研究

摘要/Abstract

摘要： ［摘要］目的分析成釉细胞瘤患者与正常人群基因表达谱芯片差异表达的基因和长链非编码RNA（long non-coding RNA，lncRNA），探讨关键lncRNA及其参与的信号通路。方法在公共数据库基因表达数据库（gene expression omnibus, GEO）中下载成釉细胞瘤相关芯片数据集GES38494及GES132472，筛选差异表达的基因及lncRNA，构建lncRNA-mRNA共表达网络并分析其参与的GO及KEGG通路，STRING数据库进行蛋白质相互作用分析并筛选核心基因。结果经差异分析共筛选出801个差异表达基因，其中差异表达的lncRNA 6个，与283个mRNA存在共表达关系。lncRNA-mRNA共表达网络中的mRNA主要参与上皮发育、皮肤发育、表皮细胞分化、角化细胞分化、角化作用等生物学功能和干细胞多能性调节通路、胰腺分泌、视黄醇代谢、轴突导向、细胞外基质-受体相互作用、黏着斑等KEGG信号通路。蛋白质-蛋白质相互作用(protein-protein interaction, PPI)分析中IVL是连接度最大的核心基因，与其共表达的lncRNA MAGI2-AS3表达下调，二者呈负相关。结论经过生物信息学分析，发现成釉细胞瘤患者lncRNA-mRNA共表达网络基因相关信号通路及蛋白质相互作用核心基因，为成釉细胞瘤治疗靶点的选择提供理论基础。

关键词: 成釉细胞瘤, 差异基因, 长链非编码RNA, 共表达网络, 信号通路

Abstract: Objective To analyze the differentially expressed genes and long non-coding RNA (lncRNA) in gene expression microarray of ameloblastoma patients and normal person, and to explore the key lncRNA and its involved signaling pathways. Methods The gene expression omnibus (GEO) microchip data set GES38494 and GES132472 of ameloblastoma were downloaded to screen the differentially expressed genes and lncRNAs. The lncRNA-mRNA co-expression network was constructed and its involved GO and KEGG pathways were analyzed. The STRING database was used for protein interaction analysis and screening of core genes. Results A total of 801 differentially expressed genes were screened out by differential analysis, among which six were differentially expressed lncRNA and co-expressed with 283 mRNAs. The mRNA in the lncRNA-mRNA co-expression network was mainly involved in biological functions such as epithelial development, skin development, epidermal cell differentiation, keratinocyte differentiation and keratinization, as well as the pluripotent regulation pathway of stem cells, pancreatic secretion, retinol metabolism, axon guidance, extracellular matrix - receptor interaction, and adhesion signaling pathway of KEGG. In PPI analysis, IVL was the core gene with the highest degree of connectivity, and the expression of its co-expressed lncRNA MAGI2-AS3 was down-regulation, showing a negative correlation. Conclusion Through bioinformatics analysis, signaling pathways that related to ameloblastoma lncRNA-mRNA co-expression network genes and core genes of protein interaction are found out, which provides a theoretical basis for target selection in ameloblastoma treatment .

Key words: ameloblastoma, differential gene, Long non-coding RNA, co-expression network, signaling pathway

中图分类号:

R739.82

傅瑜杨蓉单杰张杰林晓虎江裕程卞成玥罗颐辰. 成釉细胞瘤患者lncRNA-mRNA共表达网络分析及作用研究[J]. 口腔医学, 2020, 40(10): 904-909.

参考文献 24

[1]	Zeballos R, Bologna-Molina R, Pereira-Prado V, et al.Expression of parathyroid hormone related protein (PTHRP) in ameloblastomas[J].J Clin Exp Dent, 2018, 10(2):e172-e176
[2]	Pagella P, Catón J, Meisel CT, et al.Ameloblastomas exhibit stem cell potential,possess neurotrophic properties,and establish connections with trigeminal neurons[J].Cells, 2020, 9(3):644-
[3]	Effiom OA, Ogundana OM, Akinshipo AO, et al.Ameloblastoma: current etiopathological concepts and management[J].Oral Dis, 2018, 24(3):307-316
[4]	Hendra FN, Van Cann EM, Helder MN, et al.Global incidence and profile of ameloblastoma: A systematic review and meta-analysis[J].Oral Dis, 2020, 26(1):12-21
[5]	Jathar S, Kumar V, Srivastava J, et al.Technological Developments in lncRNA Biology[M]//Advances in Experimental Medicine and Biology. Singapore: Springer Singapore, 2017: 283-323.
[6]	Ghosal S, Das S, Chakrabarti J.Long noncoding RNAs: New players in the molecular mechanism for maintenance and differentiation of pluripotent stem cells[J].Stem Cells Dev, 2013, 22(16):2240-2253
[7]	Tsagakis I, Douka K, Birds I, et al.Long non-coding RNAs in development and disease: Conservation to mechanisms[J].J Pathol, 2020, 250(5):480-495
[8]	Batista PJ, Chang HY.Long noncoding RNAs: Cellular address codes in development and disease[J].Cell, 2013, 152(6):1298-1307
[9]	Davanian H, Balasiddaiah A, Heymann R, et al.Ameloblastoma RNA profiling uncovers a distinct non-coding RNA signature[J].Oncotarget, 2017, 8(3):4530-4542
[10]	Heikinheimo K, Kurppa KJ, Laiho A, et al.Early dental epithelial transcription factors distinguish ameloblastoma from keratocystic odontogenic tumor[J].J Dent Res, 2015, 94(1):101-111
[11]	Kondo S, Ota A, Ono T, et al.Discovery of novel molecular characteristics and cellular biological properties in ameloblastoma[J].Cancer Med, 2020, 9(8):2904-2917
[12]	Gao F, Cai Y, Kapranov P, et al.Reverse-genetics studies of lncRNAs: What we have learnt and paths forward[J]. Genome Biol, 2020, 21:93.
[13]	McDonel P, Guttman M.Approaches for understanding the mechanisms of long noncoding RNA regulation of gene expression[J].Cold Spring Harb Perspect Biol, 2019, 11(12):a032151-
[14]	Liu S, Mitra R, Zhao MM, et al.The potential roles of long noncoding RNAs (lncRNA) in glioblastoma development[J].Mol Cancer Ther, 2016, 15(12):2977-2986
[15]	Diniz MG, Fran?a JA, Vilas-Boas FAS, et al.The long noncoding RNA KIAA0125 is upregulated in ameloblastomas[J].Pathol Res Pract, 2019, 215(3):466-469
[16]	Sun Y, Niu X, Wang GN, et al.A novel lncRNA ENST00000512916 facilitates cell proliferation, migration and cell cycle progression in ameloblastoma[J]. Oncotargets Ther, 2020, 13:1519-1531.
[17]	Man HSJ, Marsden PA.LncRNAs and epigenetic regulation of vascular endothelium: Genome positioning system and regulators of chromatin modifiers[J]. Curr Opin Pharmacol, 2019, 45:72-80.
[18]	Neagu D, Escuder-de la Torre O, Vázquez-Mahía I, et al.Surgical management of ameloblastomaReview of literature[J].J Clin Exp Dent, 2019, 11(1):e70-e75
[19]	Yoithapprabhunath TR, Nirmal RM, Ganapathy N, et al.Meta-terminology of Ameloblastoma[J].J Pharm Bioallied Sci, 2019, 11(Suppl 2):S140-S145
[20]	Reimand J, Isserlin R, Voisin V, et al.Pathway enrichment analysis and visualization of omics data using g: Profiler,GSEA,Cytoscape and EnrichmentMap[J].Nat Protoc, 2019, 14(2):482-517
[21]	Subramanian A, Tamayo P, Mootha VK, et al.Gene set enrichment analysis: A knowledge-based approach for interpreting genome-wide expression profiles[J].Proc Natl Acad Sci U S A, 2005, 102(43):15545-15550
[22]	Politiek K, Loman L, Pas HH, et al.Hyperkeratotic hand eczema: Eczema or not?[J/OL]. Contact Derm, 2020[2020-05-28] DOI:10.1111/cod.13572.
[23]	Chen P, Sun S, Zeng K, et al.Exome sequencing identifies a TCF4 mutation in a Chinese pedigree with symmetrical acral keratoderma. [J]. J Eur Acad Dermatol Venereol. 2018; 32(7):1204-1208.
[24]	Man MQ, Hatano Y, Lee SH, et al.Characterization of a hapten-induced, murine model with multiple features of atopic dermatitis: structural, immunologic, and biochemical changes following single versus multiple oxazolone challenges[J]. J Invest Dermatol. 2008; 128(1):79-86.