泛癌症分析DEAH盒解旋酶16的表达及其预后意义
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摘要
目的泛癌症分析DEAH盒解旋酶16 (DHX16)的表达、预后意义及作用机制。方法利用癌症基因组图谱组织(TCGA)门户网站UALCAN泛癌症分析DHX16的表达及其与预后关系;通过蛋白之间相互作用平台InBio MapTM下载与DHX16相互作用的蛋白质谱,经DAVID 6.8进行基因本体(GO)和KEGG信号通路分析。结果 DHX16在膀胱尿路上皮癌、头颈部鳞状细胞癌、食管癌、肝脏肝细胞癌和胆管癌中高表达(均P <0.001);DHX16高表达利于膀胱尿路上皮癌预后,而不利于肾上腺皮质癌、肉瘤、脑低级别胶质瘤、肝脏肝细胞癌和急性髓样白血病的预后。DHX16相互作用蛋白主要定位于剪接体、细胞核、质膜、胞内核糖核蛋白复合体等,参与mRNA剪接、加工过程等,主要结合多聚腺苷酸RNA、核苷酸、核酸、m RNA内含子等,具有RNA解旋酶活性等功能;参与的信号通路主要包括剪接体、mRNA监测、RNA降解和RNA转运过程。结论 DHX16在膀胱尿路上皮癌、头颈部鳞状细胞癌、食管癌、肝脏肝细胞癌和胆管癌中高表达,DHX16高表达有利于膀胱尿路上皮癌预后,而不利于肾上腺皮质癌、肉瘤、脑低级别胶质瘤、肝脏肝细胞癌和急性髓样白血病预后,因此可作为上述肿瘤预后的潜在标志物。
Objective To investigate the expression and prognostic significance of DEAH-box helicase(DHX16) by pan-cancer analysis. Methods The expression and prognostic significance of DHX16 were analyzed using the UALCAN web-portal. Gene ontology and kyoto encyclopedia of genes and genomes analyses of proteins interacting with DHX16 were performed using DAVID 6.8 functional annotation software. Results DHX16 was highly expressed in bladder urothelial carcinoma,head and neck squamous cell carcinoma,esophageal carcinoma,liver hepatocellular carcinoma,and cholangiocarcinoma(all P < 0.001). Proteins interacting with DHX16 were located mainly in catalytic step 2 spliceosome,nucleoplasm,and cell membrane,and participated in mRNA splicing and processing,binding to poly(A) RNA and nucleic acids,and RNA helicase activity. Spliceosome,mRNA surveillance,RNA degradation,and transport pathways were implicated. Conclusion The high expression of DHX16 is helpful for the prognosis of bladder urothelial carcinoma prognosis,and unfavorable for prognoses of adrenocortical carcinoma,sarcoma,brain lower grade glioma,liver hepatocellular carcinoma,and acute myeloid leukemia. Thus,DHX16 may have value as a prognostic marker.
Objective To investigate the expression and prognostic significance of DEAH-box helicase(DHX16) by pan-cancer analysis. Methods The expression and prognostic significance of DHX16 were analyzed using the UALCAN web-portal. Gene ontology and kyoto encyclopedia of genes and genomes analyses of proteins interacting with DHX16 were performed using DAVID 6.8 functional annotation software. Results DHX16 was highly expressed in bladder urothelial carcinoma,head and neck squamous cell carcinoma,esophageal carcinoma,liver hepatocellular carcinoma,and cholangiocarcinoma(all P < 0.001). Proteins interacting with DHX16 were located mainly in catalytic step 2 spliceosome,nucleoplasm,and cell membrane,and participated in mRNA splicing and processing,binding to poly(A) RNA and nucleic acids,and RNA helicase activity. Spliceosome,mRNA surveillance,RNA degradation,and transport pathways were implicated. Conclusion The high expression of DHX16 is helpful for the prognosis of bladder urothelial carcinoma prognosis,and unfavorable for prognoses of adrenocortical carcinoma,sarcoma,brain lower grade glioma,liver hepatocellular carcinoma,and acute myeloid leukemia. Thus,DHX16 may have value as a prognostic marker.
引文
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[13]PAN Y,LIU H,WANG Y,et al.Associations between genetic variants in mRNA splicing-related genes and risk of lung cancer:a pathway-based analysis from published GWASs[J].Sci Rep,2017,17(7):44634.DOI:10.1038/srep44634.
[2]GENCHEVA M,KATO M,NEWO AN,et al.Contribution of DEAH-box protein DHX16 in human pre-mRNA splicing[J].Biochem J,2010,429(1):25-32.DOI:10.1042/BJ20100266.
[3]RAPPSILBER J,RYDER U,LAMOND AI,et al.Large-scale proteomic analysis of the human spliceosome[J].Genome Res,2002,12(8):1231-1245.DOI:10.1101/gr.473902.
[4]CHANDRASHEKAR DS,BASHEL B,BALASUBRAMANYA SAH,et al.UALCAN:a portal for facilitating tumor subgroup gene expression and survival analyses[J].Neoplasia,2017,19(8):649-658.DOI:10.1016/j.neo.2017.05.002.
[5]SIEGEL RL,MILLER KD,JEMAL A.Cancer statistics,2017[J].CACancer J Clin,2017,67(1):7-30.DOI:10.3322/caac.21387.
[6]MARUSYK A,POLYAK K.Tumor heterogeneity:causes and consequences[J].Biochimica Biophysica Acta,2010,1805(1):105-117.DOI:10.1038/nature20805.
[7]COLLINS FS,VARMUS H.A new initiative on precision medicine[J].NEJM,2015,372(9):793-795.DOI:10.1056/NEJMp1500523.
[8]CANCER GENOME ATLAS RESEARCH NETWORK,ANALYSISWORKING GROUP.Integrated genomic characterization of oesophageal carcinoma[J].Nature,2017,541(7636):169-175.DOI:10.1038/nature20805.
[9]PUTIRI E,PELEGRI F.The zebrafish maternal-effect gene mission impossible encodes the DEAH-box helicase Dhx16 and is essential for the expression of downstream endodermal genes[J].Dev Biol,2011,353(2):275-289.DOI:10.1016/j.ydbio.2011.03.001.
[10]CORDIN O,BANROQUES J,TANNER NK,et al.The DEAD-box protein family of RNA helicases[J].Gene,2006,15(367):17-37.
[11]BESSONOV S,ANOKHINA M,WILL CL,et al.Isolation of an active step I spliceosome and composition of its RNP core[J].Nature,2008,452(7189):846-848.DOI:10.1038/nature06842.
[12]GENCHEVA M,LIN TY,WU X,et al.Nuclear retention of unspliced pre-mRNAs by mutant DHX16/hPRP2,a spliceosomal DEAH-box protein[J].J Biol Chem,2010,285(46):35624-35632.DOI:10.1074/jbc.M110.122309.
[13]PAN Y,LIU H,WANG Y,et al.Associations between genetic variants in mRNA splicing-related genes and risk of lung cancer:a pathway-based analysis from published GWASs[J].Sci Rep,2017,17(7):44634.DOI:10.1038/srep44634.