ADARs在肿瘤中的研究进展
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摘要
RNA特异性腺苷脱氨酶(ADARs)在RNA转录后的修饰过程中发挥重要作用,是导致生物多样性的原因之一,通过对RNA编码区或非编码区相关位点的编辑,影响人类疾病的发生、发展。尽管它已成为多种疾病研究中的热点,但其完整的生物学意义尚未完全阐明。ADARs的表达失衡与人类肿瘤的进展及肿瘤患者的预后密切相关,但是,到目前为止,其确切的作用机制尚未完全阐明。因此,通过对ADARs及其编辑位点的进一步研究,在转录后水平阐明肿瘤发生的潜在机制,可以为肿瘤的诊断、治疗新方法的探索提供理论基础。
Adenosine deaminase acting on RNA(ADARs) plays an important role in the process of RNA modification after its transcription,which is one of the leading causes of biodiversity.It has effects on the development of human disease through affecting relevant sites in both coding and non-coding regions of the transcriptome.Although it has become a hot spot in a variety of researches,its biological significance has not been fully elucidated.Imbalanced expression of ADARs has shown a close relation with the cancer progress and cancer patients,prognosis.However,the exact mechanism is still not completely elucidated.Thus,further researches about ADARs and its editing sites are needed to elucidate the underlying mechanisms at the post-transcriptional level,which can provide theoretical basis for the exploration of new methods for cancer diagnosis and treatment.
Adenosine deaminase acting on RNA(ADARs) plays an important role in the process of RNA modification after its transcription,which is one of the leading causes of biodiversity.It has effects on the development of human disease through affecting relevant sites in both coding and non-coding regions of the transcriptome.Although it has become a hot spot in a variety of researches,its biological significance has not been fully elucidated.Imbalanced expression of ADARs has shown a close relation with the cancer progress and cancer patients,prognosis.However,the exact mechanism is still not completely elucidated.Thus,further researches about ADARs and its editing sites are needed to elucidate the underlying mechanisms at the post-transcriptional level,which can provide theoretical basis for the exploration of new methods for cancer diagnosis and treatment.
引文
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[27]Chan TH,Qamra A,Tan KT,et al.ADAR-mediated RNA editing predicts progression and prognosis of Gastric Cancer[J].Gastroenterology,2016,151(4):637-650.
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[30]Martinez HD,Jasavala RJ,Hinkson I,et al.RNA editing of androgen receptor gene transcripts in prostate cancer cells[J].J Biol Chem,2008,283(44):29938-29949.
[31]Mo F,Wyatt AW,Sun Y,et al.Systematic identification and characterization of RNA editing in prostate tumors[J].PLo S One,2014,9(7):e101431.
[32]Salameh A,Lee AK,Cardó-Vila M,et al.PRUNE2 is a human prostate cancer suppressor regulated by the intronic long noncoding RNAPCA3[J].Proc Natl Acad Sci U S A,2015,112(27):8403-8408.
[33]Ma CH,Chong JH,Guo Y,et al.Abnormal expression of ADAR1isoforms in Chinese pediatric acute leukemias[J].Biochem Biophys Res Commun,2011,406(2):245-251.
[34]Steinman RA,Yang Q,Gasparetto M,et al.Deletion of the RNAediting enzyme ADAR1 causes regression of established chronic myelogenous leukemia in mice[J].Int J Cancer,2013,132(8):1741-1750.
[35]Allegra D,Bilan V,Garding A,et al.Defective DROSHA processing contributes to downregulation of MiR-15/-16 in chronic lymphocytic leukemia[J].Leukemia,2014,28(1):98-107.
[36]Kuang L,Lv G,Wang B,et al.Overexpression of adenosine deaminase acting on RNA 1 in chordoma tissues is associated with chordoma pathogenesis by reducing miR125a and miR10a expression[J].Mol Med Rep,2015,12(1):93-98.
[37]Galeano F,Leroy A,Rossetti C,et al.Human BLCAP transcript:new editing events in normal and cancerous tissues[J].INT J CANCER,2010,127(1):127-137.
[38]王岩,陈丽波,魏君,等.ADAR mRNA在胰腺癌及癌旁组织中的表达及意义[J].中国实验诊断学,2011,15(2):328-329.
[39]Holley RW.Structure of an alanine transfer ribonucleic acid[J].JAMA,1965,194(8):868-871.
[2]Li JB,Church GM.Deciphering the functions and regulation of brain-enriched A-to-I RNA editing[J].Nat Neurosci,2013,16(11):1518-1522.
[3]Slotkin W,Nishikura K.Adenosine-to-inosine RNA editing and human disease[J].Genome Med,2013,5(11):105-118.
[4]Tariq A,Jantsch MF.Transcript Diversification in the Nervous System:A to I RNA Editing in CNS Function and Disease Development[J].Front Neurosci,2012,6:99.
[5]乔俊静.ADAR1在食管鳞状细胞癌中的表达及其功能的初步研究[D].郑州:郑州大学,2013.
[6]Samuel CE.Adenosine deaminases acting on RNA(ADARs)are both antiviral and proviral[J].Virology,2011,411(2):180-193.
[7]Gaisler-Salomon I,Kravitz E,Feiler Y,et al.Hippocampus-specific deficiency in RNA editing of Glu A2 in Alzheimer's disease[J].Neurobiol Aging,2014,35(8):1785-1791.
[8]Sasaki S,Yamashita T,Shin K.Autophagy in spinal motor neurons of conditional ADAR2-knockout mice:An implication for a role of calcium in increased autophagy flux in ALS[J].Neurosci Lett,2015,598:79-84.
[9]Tomaselli S,Bonamassa B,Alisi A,et al.ADAR Enzyme and miRNA Story:A Nucleotide that Can Make the Difference[J].Int J Mol Sci,2013,14(11):22796-22816.
[10]Chen CX,Cho DS,Wang Q,et al.A third member of the RNAspecific adenosine deaminase gene family,ADAR3,contains both single-and double-stranded RNA binding domains[J].RNA,2000,6(5):755-767.
[11]Engwer C,Knappitsch M,Surulescu C.A multiscale model for glioma spread including cell-tissue interactions and proliferation[J].Math Biosci Eng,2016,13(2):443-460.
[12]Yang B,Hu P,Lin X,et al.PTBP1 induces ADAR1 p110 isoform expression through IRES-like dependent translation control and influences cell proliferation in gliomas[J].Cell Mol Life Sci,2015,72(22):4383-4397.
[13]刘藻滨.ADAR1在胶质瘤中的表达及其功能研究[D].西安:第四军医大学,2013.
[14]Tomaselli S,Galeano F,Alon S,et al.Modulation of microRNA editing,expression and processing by ADAR2 deaminase in glioblastoma[J].Genome Biol,2015,16(1):5.
[15]Maas S,Patt S,Schrey M,et al.Underediting of glutamate receptor GluR-B mRNA in malignant gliomas[J].Proc Natl Acad Sci U S A,2001,98(25):14687-14692.
[16]Tomaselli S,Galeano F,Massimi L,et al.ADAR2 editing activity in newly diagnosed versus relapsed pediatric high-grade astrocytomas[J].BMC Cancer,2013,13:255.
[17]Galeano F,Rossetti C,Tomaselli S,et al.ADAR2-editing activity inhibits glioblastoma growth through the modulation of the CDC14B/Skp2/p21/p27 axis[J].Oncogene,2013,32(8):998-1009.
[18]Choudhury Y,Tay FC,Lam DH,et al.Attenuated adenosineto-inosine editing of microRNA-376a*promotes invasiveness of glioblastoma cells[J].J Clin Invest,2012,122(11):4059-4076.
[19]Paz N,Levanon EY,Amariglio N,et al.Altered adenosine-to-inosine RNA editing in human cancer[J].Genome Res,2007,17(11):1586-1595.
[20]Choi KS,Suh YH,Kim WH,et al.Stable siRNA-mediated silencing of antizyme inhibitor:regulation of ornithine decarboxylase activity[J].Biochem Biophys Res Commun,2005,328(1):206-212.
[21]Chen L,Li Y,Lin CH,et al.Recoding RNA editing of antizyme inhibitor 1 predisposes to hepatocellular carcinoma[J].Nat Med,2013,2(19):209-216.
[22]Valles I,Pajares MJ,Segura V,et al.Identification of novel deregulated RNA metabolism-related genes in non-small cell lung cancer[J].PLo S One,2012,7(8):e42086.
[23]Han SW,Kim HP,Shin JY,et al.RNA editing in RHOQ promotes invasion potential in colorectal cancer[J].J Exp Med,2014,211(4):613-621.
[24]Mizuguchi Y,Mishima T,Yokomuro S,et al.Sequencing and Bioinformatics-Based Analyses of the microRNA Transcriptome in Hepatitis B-Related Hepatocellular Carcinoma[J].PLo S One,2011,6(1):e15304.
[25]Liu WH,Chen CH,Yeh KH,et al.ADAR2-mediated editing of miR-214 and miR-122 precursor and antisense RNA transcripts in liver cancers[J].PLo S One,2013,12(8),e81922.
[26]Chan TH,Lin CH,Qi L,et al.A disrupted RNA editing balance mediated by ADARs(Adenosine deaminase that act on RNA)in human hepatocellular carcinoma[J].Gut,2014,63(5):832-843.
[27]Chan TH,Qamra A,Tan KT,et al.ADAR-mediated RNA editing predicts progression and prognosis of Gastric Cancer[J].Gastroenterology,2016,151(4):637-650.
[28]张广,姜涛,田宇,等.RNA编辑酶在结直肠癌组织标本中的表达[J].中国实验诊断学,2010,14(7):1047-1048.
[29]Fumagalli D,Gacquer D,RothéF,et al.Principles governing A-to-I RNA editing in the breast cancer transcriptome[J].Cell Rep,2015,13(2):277-289.
[30]Martinez HD,Jasavala RJ,Hinkson I,et al.RNA editing of androgen receptor gene transcripts in prostate cancer cells[J].J Biol Chem,2008,283(44):29938-29949.
[31]Mo F,Wyatt AW,Sun Y,et al.Systematic identification and characterization of RNA editing in prostate tumors[J].PLo S One,2014,9(7):e101431.
[32]Salameh A,Lee AK,Cardó-Vila M,et al.PRUNE2 is a human prostate cancer suppressor regulated by the intronic long noncoding RNAPCA3[J].Proc Natl Acad Sci U S A,2015,112(27):8403-8408.
[33]Ma CH,Chong JH,Guo Y,et al.Abnormal expression of ADAR1isoforms in Chinese pediatric acute leukemias[J].Biochem Biophys Res Commun,2011,406(2):245-251.
[34]Steinman RA,Yang Q,Gasparetto M,et al.Deletion of the RNAediting enzyme ADAR1 causes regression of established chronic myelogenous leukemia in mice[J].Int J Cancer,2013,132(8):1741-1750.
[35]Allegra D,Bilan V,Garding A,et al.Defective DROSHA processing contributes to downregulation of MiR-15/-16 in chronic lymphocytic leukemia[J].Leukemia,2014,28(1):98-107.
[36]Kuang L,Lv G,Wang B,et al.Overexpression of adenosine deaminase acting on RNA 1 in chordoma tissues is associated with chordoma pathogenesis by reducing miR125a and miR10a expression[J].Mol Med Rep,2015,12(1):93-98.
[37]Galeano F,Leroy A,Rossetti C,et al.Human BLCAP transcript:new editing events in normal and cancerous tissues[J].INT J CANCER,2010,127(1):127-137.
[38]王岩,陈丽波,魏君,等.ADAR mRNA在胰腺癌及癌旁组织中的表达及意义[J].中国实验诊断学,2011,15(2):328-329.
[39]Holley RW.Structure of an alanine transfer ribonucleic acid[J].JAMA,1965,194(8):868-871.