RBM8A与恶性肿瘤相关性研究进展
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摘要
目的核糖核酸结合基序蛋白8A(RNA-binding motif protein 8A,RBM8A),又名Y14,是高度保守的RNA结合基序(RNA binding motif,RBM)蛋白家族的成员之一,在生物体内对基因的表达和信号转导通路具有重要的调控作用。本研究对RBM8A与恶性肿瘤相关的研究现状,以及RBM8A与恶性肿瘤发生机制、肿瘤诊断和预后的作用进行综述。方法以"RBM8A,肿瘤"为关键词,应用PubMed及CNKI期刊全文数据库检索系统,检索2000-06-2018-08的相关文献,共检索到英文文献155篇,中文文献4篇。纳入标准:(1)RBM8A的生物活性及其生理功能;(2)RBM8A的异常表达对恶性肿瘤发生发展的影响;(3)RBM8A在恶性肿瘤的诊断、治疗和预后中的作用。排除与本研究无关的文献,最终纳入分析33篇文献。结果 RBM8A在肝细胞癌、乳腺癌、宫颈癌、膀胱癌、多发性骨髓瘤、胸膜间皮瘤和非小细胞肺癌中高表达,通过基因表达的调控、细胞周期及活力的调控以及多条信号转导通路的调节等多个环节参与肿瘤的发生发展。结论 RBM8A的表达异常在多种恶性肿瘤的发生发展中具有重要作用;RBM8A有望成为多种恶性肿瘤诊断、治疗及其预后监测和评估的肿瘤标志物。
OBJECTIVE RNA binding motif protein 8 A(RBM8 A)(also known as Y14)is a member of the highly conserved RNA binding motif(RBM)protein family,which plays an important regulatory role in gene expression and signal transduction pathways in biological fitness.This paper aimed to review the current research status of RBM8 Arelated to malignant tumors,as well as the role of RBM8 Ain the pathogenesis,diagnosis and prognosis of malignant tumors.METHODS "RBM8 A,tumor"were searched as key Words by PubMed and CNKI series full text database retrieval system from 2000-06 to 2018-08.Totally 155 English papers 4 Chinese papers were obtained.Inclusion criteria:(1)biological activity and physiological function of RBM8 A;(2)the effect of abnormal expression of RBM8 Aon malignant tumor development and progression;(3)role of RBM8 Ain diagnosis,treatment and prognosis of malignant tumor.Excluding the literature unrelated to this study,33 papers were finally included in the analysis.RESULTS RBM8 Ais highly expressed in hepatocellular carcinoma,breast cancer,cervical cancer,bladder cancer,multiple myeloma,pleural mesothelioma,and nonsmall cell lung cancer,and is involved in the occurrence and development of tumors through the regulation of gene expression,the regulation of cell cycle and vitality,and the regulation of multiple signal transduction pathways.CONCLUSIONS Abnormal expression of RBM8 Aplays an important role in the occurrence and development of various malignant tumors.RBM8 Ais expected to be a tumor marker for diagnosis,treatment and prognosis monitoring and evaluation of multiple tumors.
OBJECTIVE RNA binding motif protein 8 A(RBM8 A)(also known as Y14)is a member of the highly conserved RNA binding motif(RBM)protein family,which plays an important regulatory role in gene expression and signal transduction pathways in biological fitness.This paper aimed to review the current research status of RBM8 Arelated to malignant tumors,as well as the role of RBM8 Ain the pathogenesis,diagnosis and prognosis of malignant tumors.METHODS "RBM8 A,tumor"were searched as key Words by PubMed and CNKI series full text database retrieval system from 2000-06 to 2018-08.Totally 155 English papers 4 Chinese papers were obtained.Inclusion criteria:(1)biological activity and physiological function of RBM8 A;(2)the effect of abnormal expression of RBM8 Aon malignant tumor development and progression;(3)role of RBM8 Ain diagnosis,treatment and prognosis of malignant tumor.Excluding the literature unrelated to this study,33 papers were finally included in the analysis.RESULTS RBM8 Ais highly expressed in hepatocellular carcinoma,breast cancer,cervical cancer,bladder cancer,multiple myeloma,pleural mesothelioma,and nonsmall cell lung cancer,and is involved in the occurrence and development of tumors through the regulation of gene expression,the regulation of cell cycle and vitality,and the regulation of multiple signal transduction pathways.CONCLUSIONS Abnormal expression of RBM8 Aplays an important role in the occurrence and development of various malignant tumors.RBM8 Ais expected to be a tumor marker for diagnosis,treatment and prognosis monitoring and evaluation of multiple tumors.
引文
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[19] Palacios IM,Gatfield D,St Johnston D,et al.An eIF4AⅢ-containing complex required for mRNA localization and nonsense-mediated mRNA decay[J].Nature,2004,427(6976):753-757.
[20] Floquet C,Deforges J,Rousset JP,et al.Rescue of non-sense mutated p53tumor suppressor gene by aminoglycosides[J].Nucleic Acids Res,2011,39(8):3350-3362.
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[25] Zindy PJ,L'Helgoualc'h A,Bonnier D,et al.Upregulation of the tumor suppressor gene menin in hepatocellular carcinomas and its significance in fibrogenesis[J].Hepatology,2006,44(5):1296-1307.
[26] Liang R,Lin Y,Ye JZ,et al.High expression of RBM8Apredicts poor patient prognosis and promotes tumor progression in hepatocellular carcinoma[J].Oncol Rep,2017,37(4):2167-2176.
[27]冉亮,涂刚,王小毅,等.Y14和Upf1在人乳腺癌细胞表达增强[J].基础医学与临床,2009,29(11):1150-1154.
[28]孔令泉,蒲莹晖,任国胜.Y14在乳腺癌组织中的表达及意义[J].中国肿瘤临床,2010,37(19):1106-1108,1114.
[29] Kim TJ,Choi JJ,Kim WY,et al.Gene expression profiling for the prediction of lymph node metastasis in patients with cervical cancer[J].Cancer Sci,2008,99(1):31-38.
[30] Carrasco DR,Tonon G,Huang Y,et al.High-resolution genomic profiles define distinct clinico-pathogenetic subgroups of multiple myeloma patients[J].Cancer Cell,2006,9(4):313-325.
[31]甘隆,卢海庆,李生华,等.RBM8A膀胱尿路上皮癌中的表达及其意义[J].新医学,2018,49(3):164-168.
[32] Sudo H,Tsuji AB,Sugyo A,et al.Knockdown of COPA,identified by loss-of-function screen,induces apoptosis and suppresses tumor growth in mesothelioma mouse model[J].Genomics,2010,95(4):210-216.
[33] Petroziello J,Yamane A,Westendorf L,et al.Suppression subtractive hybridization and expression profiling identifies a unique set of genes overexpressed in non-small-cell lung cancer[J].Oncogene,2004,23(46):7734-7745.
[2] Diem MD,Chan CC,Younis I,et al.PYM binds the cytoplasmic exonjunction complex and ribosomes to enhance translation of spliced mRNAs[J].Nat Struct Mol Biol,2007,14(12):1173-1179.
[3] Ishigaki Y,Nakamura Y,Tatsuno T,et al.Depletion of RNAbinding protein RBM8A(Y14)causes cell cycle deficiency and apoptosis in human cells[J].Exp Biol Med(Maywood),2013,238(8):889-897.
[4] Ishigaki Y,Nakamura Y,Tatsuno T,et al.RNA-binding protein RBM8A(Y14)and MAGOH localize to centrosome in human A549cells[J].Histochem Cell Biol,2014,141(1):101-109.
[5] Lu CC,Lee CC,Tseng CT,et al.Y14governs p53expression and modulates DNA damage sensitivity[J].Sci Rep,2017,7:45558.
[6] Ohbayashi N,Taira N,Kawakami S,et al.An RNA biding protein,Y14interacts with and modulates STAT3activation[J].Biochem Biophys Res Commun,2008,372(3):475-479.
[7] Togi S,Shiga K,Muromoto R,et al.Y14positively regulates TNF-induced NF-B transcriptional activity via interacting RIP1and TRADD beyond an exon junction complex protein[J].J Immunol,2013,191(3):1436-1444.
[8] Roignant JY,Treisman JE.Exon junction complex subunits are required to splice drosophila MAP kinase,a large heterochromatic gene[J].Cell,2010,143(2):238-250.
[9] Mingot JM,Kostka S,Kraft R,et al.Importin 13:a novel mediator of nuclear import and export[J].EMBO J,2001,20(14):3685-3694.
[10] Kataoka N,Diem MD,Yoshida M,et al.Specific Y14domains mediate its nucleo-cytoplasmic shuttling and association with spliced mRNA[J].Sci Rep,2011,1:92.
[11] Hsu Ia W,Hsu M,Li C,et al.Phosphorylation of Y14modulates its interaction with proteins involved in mRNA metabolism and influences its methylation[J].J Biol Chem,2005,280(41):34507-34512.
[12] Ishigaki Y,Nakamura Y,Tatsuno T,et al.Phosphorylation status of human RNA-binding protein 8Ain cells and its inhibitory regulation by Magoh[J].Exp Biol Med(Maywood),2015,240(4):438-445.
[13] Tatsuno T,Ishigaki Y.C-terminal short arginine/serine repeat sequence-dependent regulation of Y14(RBM8A)localization[J].Sci Rep,2018,8(1):612.
[14] Tange TO,Shibuya T,Jurica MS,et al.Biochemical analysis of the EJC reveals two new factors and a stable tetrameric protein core[J].RNA(New York,NY),2005,11(12):1869-1883.
[15] Michelle L,Cloutier A,Toutant J,et al.Proteins associated with the exon junction complex also control the alternative splicing of apoptotic regulators[J].Mol Cell Biol,2012,32(5):954-967.
[16] Nott A,Le Hir H,Moore MJ.Splicing enhances translation in mammalian cells:an additional function of the exon junction complex[J].Genes Dev,2004,18(2):210-222.
[17] Lee HC,Choe J,Chi S-G,et al.Exon junction complex enhances translation of spliced mRNAs at multiple steps[J].Biochem Biophys Res Commun,2009,384(3):334-340.
[18] Kim VN,Kataoka N,Dreyfuss G.Role of the nonsense-mediated decay factor hUpf3in the splicing-dependent exon-exon junction complex[J].Science(New York,NY),2001,293(5536):1832-1836.
[19] Palacios IM,Gatfield D,St Johnston D,et al.An eIF4AⅢ-containing complex required for mRNA localization and nonsense-mediated mRNA decay[J].Nature,2004,427(6976):753-757.
[20] Floquet C,Deforges J,Rousset JP,et al.Rescue of non-sense mutated p53tumor suppressor gene by aminoglycosides[J].Nucleic Acids Res,2011,39(8):3350-3362.
[21] Merz C,Urlaub H,Will CL,et al.Protein composition of human mRNPs spliced in vitro and differential requirements for mRNP protein recruitment[J].RNA(New York,NY),2007,13(1):116-128.
[22] Gehring NH,Lamprinaki S,Hentze MW,et al.The hierarchy of exon-junction complex assembly by the spliceosome explains key features of mammalian nonsense-mediated mRNA decay[EB/OL].PLoS Biol,2009,7(5):e1000120[2018-05-05].https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.1000120.
[23] Fukumura K,Wakabayashi S,Kataoka N,et al.The exon junction complex controls the efficient and faithful splicing of a subset of transcripts involved in mitotic cell-cycle progression[EB/OL].Int J Mol Sci,2016,17(8):1153[2018-05-05].https://www.mdpi.com/1422-0067/17/8/1153.
[24] Chuang TW,Lee KM,Lou YC,et al.A point mutation in the exon junction complex factor Y14disrupts its function in mRNA cap binding and translation enhancement[J].J Biol Chem,2016,291(16):8565-8574.
[25] Zindy PJ,L'Helgoualc'h A,Bonnier D,et al.Upregulation of the tumor suppressor gene menin in hepatocellular carcinomas and its significance in fibrogenesis[J].Hepatology,2006,44(5):1296-1307.
[26] Liang R,Lin Y,Ye JZ,et al.High expression of RBM8Apredicts poor patient prognosis and promotes tumor progression in hepatocellular carcinoma[J].Oncol Rep,2017,37(4):2167-2176.
[27]冉亮,涂刚,王小毅,等.Y14和Upf1在人乳腺癌细胞表达增强[J].基础医学与临床,2009,29(11):1150-1154.
[28]孔令泉,蒲莹晖,任国胜.Y14在乳腺癌组织中的表达及意义[J].中国肿瘤临床,2010,37(19):1106-1108,1114.
[29] Kim TJ,Choi JJ,Kim WY,et al.Gene expression profiling for the prediction of lymph node metastasis in patients with cervical cancer[J].Cancer Sci,2008,99(1):31-38.
[30] Carrasco DR,Tonon G,Huang Y,et al.High-resolution genomic profiles define distinct clinico-pathogenetic subgroups of multiple myeloma patients[J].Cancer Cell,2006,9(4):313-325.
[31]甘隆,卢海庆,李生华,等.RBM8A膀胱尿路上皮癌中的表达及其意义[J].新医学,2018,49(3):164-168.
[32] Sudo H,Tsuji AB,Sugyo A,et al.Knockdown of COPA,identified by loss-of-function screen,induces apoptosis and suppresses tumor growth in mesothelioma mouse model[J].Genomics,2010,95(4):210-216.
[33] Petroziello J,Yamane A,Westendorf L,et al.Suppression subtractive hybridization and expression profiling identifies a unique set of genes overexpressed in non-small-cell lung cancer[J].Oncogene,2004,23(46):7734-7745.