人鼻咽癌组织环状RNA差异表达分析
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摘要
目的环状RNA(circRNA)在肿瘤发生发展中发挥重要作用,但其与鼻咽癌的关系鲜有报道。文中旨在检测circRNA在人鼻咽癌组织及慢性鼻咽黏膜炎组织的表达谱差异。方法应用高通量circRNA芯片技术,采集2016年11月至2017年3月在广东医科大学附属医院进行活检的鼻咽癌组织和鼻咽慢性黏膜炎组织标本各3份,分析circRNA表达谱差异。通过对原始数据进行预处理、归一化,筛选出差异表达的circRNA,并对其进行聚类分析,Gene Ontology(GO)分析及KEGG Pathway分析,分析差异circRNA的功能分类及相关通路。结果鼻咽癌组织与慢性鼻咽黏膜炎组织之间共筛选出差异表达circRNA 829个,其中鼻咽癌组织中表达上调者761个,下调者68个。差异表达circRNA主要与细胞周期、细胞增殖等生物学进程有关;主要参与p53信号通路,细胞周期信号通路和DNA复制信号通路等。结论差异表达的circRNA与鼻咽癌的发生发展密切相关。
Objective Circular RNA(CircRNA) plays an important role in the carcinogenesis and development of cancers.However,the relationship between circ RNA and nasopharyngeal carcinoma(NPC) has been rarely reported.The aim of this study is to investigate the differentially expressed circ RNAs in human NPC and chronic nasopharyngeal mucositis.Methods Three NPC specimens and three chronic nasopharyngeal mucositis specimens which were diagnosed by nasopharyngeal biopsy in the Affiliated Hospital of Guangdong Medical University from November 2016 to March 2017,were enrolled in the study.The circ RNA expression profiles of those candidates were assayed by high-throughput human circ RNA microarray.After pretreatment and homogenization of the original data,the circ RNAs with differential expression were screened out and analyzed by hierarchical clustering.Moreover,Gene Ontology(GO) analysis and KEGG pathway analysis were performed to analyze the functional classification and related pathways.Results Compared with the chronic nasopharyngeal mucositis,there are a total of 829 differentially expressed circ RNAs in NPC,among which 761 were found to be up-regulated and 68 were down-regulated.Those differentially expressed circ RNAs were analyzed to be mainly related to cell cycle,cell proliferation and other biological processes;mainly involved in p53 signaling pathway,cell cycle and DNA replication signaling pathway.Conclusion Those differentially expressed circ RNAs may be associated with the tumorigenesis and development of NPC.
Objective Circular RNA(CircRNA) plays an important role in the carcinogenesis and development of cancers.However,the relationship between circ RNA and nasopharyngeal carcinoma(NPC) has been rarely reported.The aim of this study is to investigate the differentially expressed circ RNAs in human NPC and chronic nasopharyngeal mucositis.Methods Three NPC specimens and three chronic nasopharyngeal mucositis specimens which were diagnosed by nasopharyngeal biopsy in the Affiliated Hospital of Guangdong Medical University from November 2016 to March 2017,were enrolled in the study.The circ RNA expression profiles of those candidates were assayed by high-throughput human circ RNA microarray.After pretreatment and homogenization of the original data,the circ RNAs with differential expression were screened out and analyzed by hierarchical clustering.Moreover,Gene Ontology(GO) analysis and KEGG pathway analysis were performed to analyze the functional classification and related pathways.Results Compared with the chronic nasopharyngeal mucositis,there are a total of 829 differentially expressed circ RNAs in NPC,among which 761 were found to be up-regulated and 68 were down-regulated.Those differentially expressed circ RNAs were analyzed to be mainly related to cell cycle,cell proliferation and other biological processes;mainly involved in p53 signaling pathway,cell cycle and DNA replication signaling pathway.Conclusion Those differentially expressed circ RNAs may be associated with the tumorigenesis and development of NPC.
引文
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[2]Fles R,Bos A,Supriyati,et al.The role of Indonesian patients'health behaviors in delaying the diagnosis of nasopharyngeal carcinoma[J].BMC Public Health,2017,17(1):510.
[3]Chen X,Zhu X,Liang Z,et al.Long-term outcomes of neoadjuvant chemotherapy followed by concurrent chemoradiotherapy(CCRT)vs CCRT alone for nasopharyngeal carcinoma in the era of intensity-modulated radiation therapy using propensity score matching method[J].Onco Targets Ther,2017,10:2909-2921.
[4]Guo JU,Agarwal V,Guo H,et al.Expanded identification and characterization of mammalian circular RNAs[J].Genome Biol,2014,15(7):409.
[5]Ledford H.Circular RNAs throw genetics for a loop[J].Nature,2013,494(7438):415.
[6]Zhao Z,Li X,Jian D,et al.Hsa_circ_0054633 in peripheral blood can be used as a diagnostic biomarker of pre-diabetes and type 2 diabetes mellitus[J].Acta Diabetol,2017,54(3):237-245.
[7]Holdt LM,Stahringer A,Sass K,et al.Circular non-coding RNA ANRIL modulates ribosomal RNA maturation and atherosclerosis in humans[J].Nat Commun,2016,7:12429.
[8]Ren S,Xin Z,Xu Y,et al.Construction and analysis of circular RNA molecular regulatory networks In liver cancer[J].Cell Cycle,2017,16(22):2204-2211.
[9]Shao Y,Li J,Lu R,et al.Global circular RNA expression profile of human gastric cancer and its clinical significance[J].Cancer Med,2017,6(6):1173-1180.
[10]Memczak S,Jens M,Elefsinioti A,et al.Circular RNAs are a large class of animal RNAs with regulatory potency[J].Nature,2013,495(7441):333-338.
[11]Li Y,Zheng Q,Bao C,et al.Circular RNA is enriched and stable in exosomes:a promising biomarker for cancer diagnosis[J].Cell Res,2015,25(8):981-984.
[12]Han B,Chao J,Yao H.Circular RNA and its mechanisms in disease:From the bench to the clinic[J].Pharmacol Ther,2018,187:31-44.
[13]玄丽佳,孙亚男.环状RNA的研究进展[J].医学研究生学报,2016,29(2):201-205.
[14]Salzman J,Gawad C,Wang PL,et al.Circular RNAs are the predominant transcript isoform from hundreds of human genes in diverse cell types[J].PLo S One,2012,7(2):e30733.
[15]Jeck WR,Sorrentino JA,Wang K,et al.Circular RNAs are abundant,conserved,and associated with ALU repeats[J].RNA,2013,19(2):141-157.
[16]Hansen TB,Jensen TI,Clausen BH,et al.Natural RNA circles function as efficient micro RNA sponges[J].Nature,2013,495(7441):384-388.
[17]Ashwal-Fluss R,Meyer M,Pamudurti NR,et al.circ RNA biogenesis competes with pre-m RNA splicing[J].Mol Cell,2014,56(1):55-66.
[18]Nazer E,Lei EP.Modulation of chromatin modifying complexes by noncoding RNAs in trans[J].Curr Opin Genet Dev,2014,25:68-73.
[19]Chen LL,Yang L.Regulation of circ RNA biogenesis[J].RNA Biol,2015,12(4):381-388.
[20]Li Z,Huang C,Bao C,et al.Exon-intron circular RNAs regulate transcription in the nucleus[J].Nat Struct Mol Biol,2015,22(3):256-264.
[21]Legnini I,Di Timoteo G,Rossi F,et al.Circ-ZNF609 Is a Circular RNA that Can Be Translated and Functions in Myogenesis[J].Mol Cell,2017,66(1):22-37.
[22]Chen LL.The biogenesis and emerging roles of circular RNAs[J].Nat Rev Mol Cell Biol,2016,17(4):205-211.
[23]邓齐文,许晔琼,王书奎.长链非编码RNA多态性与肿瘤相关性的研究[J].医学研究生学报,2014,27(3):303-306.
[24]Li P,Chen S,Chen H,et al.Using circular RNA as a novel type of biomarker in the screening of gastric cancer[J].Clin Chim Acta,2015,444:132-136.
[25]Li P,Chen H,Chen S,et al.Circular RNA 0000096 affects cell growth and migration in gastric cancer[J].Br J Cancer,2017,116(5):626-633.
[26]Xuan L,Qu L,Zhou H,et al.Circular RNA:a novel biomarker for progressive laryngeal cancer[J].Am J Transl Res,2016,8(2):932-939.
[27]Qin M,Liu G,Huo X,et al.Hsa_circ_0001649:A circular RNA and potential novel biomarker for hepatocellular carcinoma[J].Cancer Biomark,2016,16(1):161-169.
[28]Li F,Zhang L,Li W,et al.Circular RNA ITCH has inhibitory effect on ESCC by suppressing the Wnt/beta-catenin pathway[J].Oncotarget,2015,6(8):6001-6013.
[29]Wang X,Zhang Y,Huang L,et al.Decreased expression of hsa_circ_001988 in colorectal cancer and its clinical significances[J].Int J Clin Exp Pathol,2015,8(12):16020-16025.
[30]Yang Y,Gao X,Zhang M,et al.Novel Role of FBXW7 Circular RNA in Repressing Glioma Tumorigenesis[J].J Natl Cancer Inst,2018,110(3).
[31]Leucci E,Vendramin R,Spinazzi M,et al.Melanoma addiction to the long non-coding RNA SAMMSON[J].Nature,2016,531(7595):518-522.