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完整後設資料紀錄
DC 欄位 | 值 | 語言 |
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dc.contributor.advisor | 阮雪芬(Hsueh-Fen Juan) | |
dc.contributor.author | Tz-Wen Yang | en |
dc.contributor.author | 楊紫文 | zh_TW |
dc.date.accessioned | 2021-06-17T01:42:59Z | - |
dc.date.available | 2020-08-03 | |
dc.date.copyright | 2017-08-03 | |
dc.date.issued | 2017 | |
dc.date.submitted | 2017-07-27 | |
dc.identifier.citation | Alexander Valencia C, Ju W & Liu R (2007) Matrin 3 is a Ca2+/calmodulin-binding protein cleaved by caspases. Biochem. Biophys. Res. Commun. 361: 281–286
Askarian-Amiri ME, Crawford J, French JD, Smart CE, Smith MA, Clark MB, Ru K, Mercer TR, Thompson ER, Lakhani SR, Vargas AC, Campbell IG, Brown MA, Dinger ME & Mattick JS (2011) SNORD-host RNA Zfas1 is a regulator of mammary development and a potential marker for breast cancer. RNA 17: 878–891 Basaki Y, Taguchi K, Izumi H, Murakami Y, Kubo T, Hosoi F, Watari K, Nakano K, Kawaguchi H, Ohno S, Kohno K, Ono M & Kuwano M (2010) Y-box binding protein-1 (YB-1) promotes cell cycle progression through CDC6-dependent pathway in human cancer cells. Eur. J. Cancer 46: 954–965 Bolón-Canedo V, Sánchez-Maroño N, Alonso-Betanzos A, Benítez JM & Herrera F (2014) A review of microarray datasets and applied feature selection methods. Inf. Sci. (Ny). 282: 111–135 Brodeur GM (2003) Neuroblastoma: biological insights into a clinical enigma. Nat. Rev. Cancer 3: 203–216 Brodeur GM & Bagatell R (2014) Mechanisms of neuroblastoma regression. Nat. Publ. Gr. 11: 704-713 Buechner J & Einvik C (2012) N-myc and Noncoding RNAs in Neuroblastoma. Mol. Cancer Res. 10: 1243–1253 Cai C, Huo Q, Wang X, Chen B & Yang Q (2017) SNHG16 contributes to breast cancer cell migration by competitively binding miR-98 with E2F5. Biochem. Biophys. Res. Commun. 485: 272-278 Carlevaro-Fita J, Rahim A, Vardy LA, Johnson R, Guigó R, Vardy LA & Johnson R (2016) Cytoplasmic long noncoding RNAs are frequently bound to and degraded at ribosomes in human cells. RNA 22: 1–16 Carpenter EL & Mosse YP (2012) Targeting ALK in neuroblastoma--preclinical and clinical advancements. Nat Rev Clin Oncol 9: 391–399 Chen L, Iraci N, Gherardi S, Gamble LD, Wood KM, Perini G, Lunec J & Tweddle DA (2010) p53 Is a Direct Transcriptional Target of MYCN in Neuroblastoma. Cancer Res. 70: 1377-1388 Cheung NK & Dyer MA (2013) Neuroblastoma: developmental biology, cancer genomics and immunotherapy. Nat. Rev. Cancer 13: 397–411 Christiansen H & Christiansen NM (2015) Progressive neuroblastoma : innovation and novel therapeutic strategies. Pediatr. Adolesc. Med. 20: 59-80 Cui Y, Zhang F, Zhu C, Geng L, Tian T, Liu H, Cui Y, Zhang F, Zhu C, Geng L, Tian T & Liu H (2017) Upregulated lncRNA SNHG1 contributes to progression of non-small cell lung cancer through inhibition of miR-101-3p and activation of Wnt/β-catenin signaling pathway. Oncotarget 5: 17785–17794 Decock A, Ongenaert M, De Wilde B, Brichard B, Noguera R, Speleman F & Vandesompele J (2016) Stage 4S neuroblastoma tumors show a characteristic DNA methylation portrait. Epigenetics 11: 761–771 Devaux Y, Zangrando J, Schroen B, Creemers EE, Pedrazzini T, Chang C-P, Dorn GW, Thum T & Heymans S (2015) Long noncoding RNAs in cardiac development and ageing. Nat. Rev. Cardiol. 12: 415–425 Dupin E, Creuzet S & Douarin NM Le (2013) The Contribution of the Neural Crest to the Vertebrate Body. Adv. Exp. Med. Biol. 589: 96-119 Fan L, Jones SN, Padden C, Shen Q & Newburger PE (2006) Nuclease sensitive element binding protein 1 gene disruption results in early embryonic lethality. J. Cell. Biochem. 99: 140–145 Gallego-Iradi MC, Clare AM, Brown HH, Janus C, Lewis J & Borchelt DR (2015) Subcellular Localization of Matrin 3 Containing Mutations Associated with ALS and Distal Myopathy. PLoS One 10: 142-144 Geuens T, Bouhy D & Timmerman V (2016) The hnRNP family: insights into their role in health and disease. Hum. Genet. 135: 851–867 Gray JC & Kohler JA (2009) Immunotherapy for neuroblastoma: Turning promise into reality. Pediatr. Blood Cancer 53: 931–940 Gu L, Zhang H, He J, Li J, Huang M & Zhou M (2012) MDM2 regulates MYCN mRNA stabilization and translation in human neuroblastoma cells. Oncogene 31: 1342–1353 Guglielmi L, Cinnella C, Nardella M, Maresca G, Valentini a, Mercanti D, Felsani a & D’Agnano I (2014) MYCN gene expression is required for the onset of the differentiation programme in neuroblastoma cells. Cell Death Dis. 5: e1081 Gustafson WC & Weiss WA (2010) Myc proteins as therapeutic targets. Oncogene 29: 1249–1259 Hisada-Ishii S, Ebihara M, Kobayashi N & Kitagawa Y (2007) Bipartite nuclear localization signal of matrin 3 is essential for vertebrate cells. Biochem. Biophys. Res. Commun. 354: 72–76 Hsu C-L, Chang H-Y, Chang J-Y, Hsu W-M, Huang H-C & Juan H-F (2016) Unveiling MYCN regulatory networks in neuroblastoma via integrative analysis of heterogeneous genomics data. Oncotarget 7: 36293–36310 Huang M & Weiss WA (2013) Neuroblastoma and MYCN. Cold Spring Harb Perspect Med. 10: a014415 Huang W, Thomas B, Flynn RA, Gavzy SJ, Wu L, Kim S V., Hall JA, Miraldi ER, Ng CP, Rigo FW, Meadows S, Montoya NR, Herrera NG, Domingos AI, Rastinejad F, Myers RM, Fuller-Pace F V., Bonneau R, Chang HY, Acuto O, et al (2015) DDX5 and its associated lncRNA Rmrp modulate TH17 cell effector functions. Nature 528: 517–522 Illiam W, Oods GW, Ie RU-N, Ao G, Onathan J, Huster JS, Eslie L, Obison LR, Ark M, Ernstein B, Heila S, Eitzman W, Reta G, Unin B, Sra I, Evy L, Osee J, Rossard B, Eoffrey G, Ougherty D, et al (2002) Screening of infants and mortality due to neuroblastoma. N. Engl. J. Med. 14: 1041-1046 Jia J, Li F, Tang X-S, Xu S, Gao Y, Shi Q, Guo W, Wang X, He D & Guo P (2016) Long noncoding RNA DANCR promotes invasion of prostate cancer through epigenetically silencing expression of TIMP2/3. Oncotarget 7: 37868–37881 Kiss T (2002) Small Nucleolar RNAs: An Abundant Group of Noncoding RNAs with Diverse Cellular Functions. Cell 109: 145–148 Kohno K, Izumi H, Uchiumi T, Ashizuka M & Kuwano M (2003) The pleiotropic functions of the Y-box-binding protein, YB-1. BioEssays 25: 691–698 Lasham A, Print CG, Woolley AG, Dunn SE & Braithwaite AW (2013) YB-1: oncoprotein, prognostic marker and therapeutic target. Biochem. J 449: 11–23 Li T, Xie J, Shen C, Cheng D, Shi Y, Wu Z, Deng X, Chen H, Shen B, Peng C, Li H, Zhan Q & Zhu Z (2015) Amplification of long noncoding RNA ZFAS1 promotes metastasis in hepatocellular carcinoma. Cancer Res. 75: 3181–3191 Li Z, Chao T-C, Chang K-Y, Lin N, Patil VS, Shimizu C, Head SR, Burns JC & Rana TM (2014) The long noncoding RNA THRIL regulates TNFα expression through its interaction with hnRNPL. Proc. Natl. Acad. Sci. U. S. A. 111: 1002–1007 Lorenzen JM & Thum T (2016) Long noncoding RNAs in kidney and cardiovascular diseases. Nat. Rev. Nephrol. 12: 360–373 Lu X, Pearson A & Lunec J (2003) The MYCN oncoprotein as a drug development target. Cancer Lett. 197: 125–130 Maris JM (2010) Recent Advances in Neuroblastoma. N. Engl. J. Med. 362: 2202–2211 Matthay KK, Maris JM, Schleiermacher G, Nakagawara A, Mackall CL, Diller L & Weiss WA (2016) Neuroblastoma. Nat. Rev. Dis. Prim. 2: 16078 Mercer TR, Dinger ME & Mattick JS (2009) Long non-coding RNAs: insights into functions. Nat. Rev. Genet. 10: 155–159 Mercer TR & Mattick JS (2013) Structure and function of long noncoding RNAs in epigenetic regulation. Nat. Publ. Gr. 20: 300–307 Mortazavi A, Williams BA, McCue K, Schaeffer L & Wold B (2008) Mapping and quantifying mammalian transcriptomes by RNA-Seq. Nat. Methods 5: 621–628 Mourtada-Maarabouni M, Pickard M, Hedge V, Farzaneh F & Williams G (2009) GAS5, a non-protein-coding RNA, controls apoptosis and is downregulated in breast cancer. Oncogene 28373: 195–208 Nicolai S, Pieraccioli M, Peschiaroli A, Melino G & Raschella G (2015) Neuroblastoma: oncogenic mechanisms and therapeutic exploitation of necroptosis. Cell Death Dis 6: e2010 Park JR, Bagatell R, London WB, Maris JM, Cohn SL, Mattay KM & Hogarty M (2013) Children’s Oncology Group’s 2013 blueprint for research: Neuroblastoma. Pediatr. Blood Cancer 60: 985–993 Przygodzka P, Boncela J & Cierniewski CS (2011) Matrin 3 as a key regulator of endothelial cell survival. Exp. Cell Res. 317: 802–811 Qi P & Du X (2013) The long non-coding RNAs, a new cancer diagnostic and therapeutic gold mine. Mod. Pathol. 26: 155–165 Quinn JJ & Chang HY (2016) Unique features of long non-coding RNA biogenesis and function. Nat. Rev. Genet. 17: 47–62 Rajan P, Dalgliesh C, Bourgeois CF, Heiner M, Emami K, Clark EL, Bindereif A, Stevenin J, Robson CN, Leung HY & Elliott DJ (2009) Proteomic identification of heterogeneous nuclear ribonucleoprotein L as a novel component of SLM/Sam68 Nuclear Bodies. BMC Cell Biol. 10: 82 van Riggelen J, Yetil A & Felsher DW (2010) MYC as a regulator of ribosome biogenesis and protein synthesis. Nat. Rev. Cancer 10: 301–309 Ruan X, Li P, Cangelosi A, Yang L & Cao H (2016) A Long Non-coding RNA, lncLGR, Regulates Hepatic Glucokinase Expression and Glycogen Storage during Fasting Cell Reports Report A Long Non-coding RNA, lncLGR, Regulates Hepatic Glucokinase Expression and Glycogen Storage during Fasting. Cell Rep. 14: 1867–1875 Sahu D, Hsu C, Lin C, Yang T, Hsu W, Ho S, Juan H & Huang H (2016) Co-expression analysis identifies long noncoding RNA SNHG1 as a novel predictor for event-free survival in neuroblastoma. Oncotarget. 36: 58022-58037 Sassolas A, Leca-Bouvier BD & Blum LJ (2008) DNA Biosensors and Microarrays. Chem. Rev. 108: 109–139 Shen Y, Liu S, Fan J, Jin Y, Tian B, Zheng X & Fu H (2017) Nuclear retention of the lncRNA SNHG1 by doxorubicin attenuates hnRNPC–p53 protein interactions. EMBO Rep. 18: 536-548 Shi X, Sun M, Liu H, Yao Y, Kong R, Chen F & Song Y (2015) A critical role for the long non-coding RNA GAS5 in proliferation and apoptosis in non-small-cell lung cancer. Mol. Carcinog. 54: 1-12 Strenger V, Kerbl R, Dornbusch HJ, Ladenstein R, Ambros PF, Ambros IM & Urban C (2007) Diagnostic and prognostic impact of urinary catecholamines in neuroblastoma patients. Pediatr. Blood Cancer 48: 504–509 Sun M, Jin F, Xia R, Kong R, Li J, Xu T, Liu Y, Zhang E, Liu X & De W (2014) Decreased expression of long noncoding RNA GAS5 indicates a poor prognosis and promotes cell proliferation in gastric cancer. BMC Cancer 14: 319 Wang KC & Chang HY (2011) Molecular Mechanisms of Long Noncoding RNAs. Mol. Cell 43: 904–914 Wang L & Li PCH (2011) Microfluidic DNA microarray analysis: A review. Anal. Chim. Acta 687: 12–27 Wang Z, Gerstein M & Snyder M (2009) RNA-Seq: a revolutionary tool for transcriptomics. Nat. Rev. Genet. 10: 57–63 You J, Fang N, Gu J, Zhang Y, Li X, Zu L & Zhou Q (2014) Noncoding RNA small nucleolar RNA host gene 1 promote cell proliferation in nonsmall cell lung cancer. Indian J. Cancer 51 Suppl 3: 99–102 Zhang M, Wang W, Li T, Yu X, Zhu Y, Ding F, Li D & Yang T (2016) Long noncoding RNA SNHG1 predicts a poor prognosis and promotes hepatocellular carcinoma tumorigenesis. Biomed. Pharmacother. 80: 73–79 Zhao S, Fung-Leung W-P, Bittner A, Ngo K, Liu X & Carstens J (2014) Comparison of RNA-Seq and Microarray in Transcriptome Profiling of Activated T Cells. PLoS One 9: e78644 Zhao X, Li D, Pu J, Mei H, Yang D, Xiang X, Qu H, Huang K, Zheng L & Tong Q (2016) CTCF cooperates with noncoding RNA MYCNOS to promote neuroblastoma progression through facilitating MYCN expression. Oncogene 35: 3565–3576 | |
dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/67665 | - |
dc.description.abstract | 神經母細胞瘤(neuroblastoma) 是一種好發於兒童的癌症,並且在臨床上被診斷出有不同的表徵及惡化程度,已知跟基因的突變機制有關並且會導致疾病的產生,其中之一為MYCN轉錄基因的異常放大。長鏈非編碼核糖核酸為長於200鹼基對類似訊息核糖核酸,但卻不會轉譯出蛋白質,其功能之一為引導蛋白質(例如: 轉錄因子)到它的標的蛋白質。由於長鏈非編碼核糖核酸 (long non-coding RNA)和MYCN轉錄基因與惡性神經母細胞瘤之間的關係仍不明確。在本研究中,我們結合核糖核酸測序(RNA-sequencing)與微陣列(Microarray)資料庫的基因表現調控網路,找到在神經母細胞瘤當中由MYCN致癌轉錄因子所調控的長鏈非編碼核糖核酸基因。我們發現small nucleolar RNA host gene 1 (SNHG1) 的表現量差異跟MYCN轉錄基因的異常放大表現量呈現高度的正相關;同時亦發現SNHG1表現較高的病人具有較差的預後。另一方面,我們利用即時聚合酶鏈式反應(qRT−PCR)證明SNHG1的表現量在MYCN異常放大神經母細胞瘤細胞株與MYCN非異常放大神經母細胞瘤細胞株具有表現量差異性。此外,在MYCN異常放大神經母細胞瘤細胞株中抑制MYCN的表現量後,SNHG1的表現量也隨之下降。SNHG1表現愈高預後越差。因此我們為了了解SNHG1的功能,利用核糖核酸蛋白質拉下測定實驗 (RNA-protein pull down assay)並結合液相層析串聯式質譜儀 (LC-MS/MS)測定蛋白身份,以得知與其交互作用的蛋白。最後,透過進一步的結合基序分析 (binding motif analysis)得知Matrin3, YBX1以及DDX5 可能會與SNHG1結合,並且利用西方點墨法(Western blot)證實Matrin 3會與SNHG1形成結合體。除此之外,我們進一步利用RNA免疫沉澱法也證實Matrin 3會與SNHG1直接結合。很多研究顯示Matrin 3是一種細胞骨架,我們猜測可能會與SNHG1形成結合體之後,參與調控神經母細胞瘤的細胞週期。本研究讓我們更深入瞭解SNHG1可能的功能,期望可以對神經母細胞瘤的治療發展有所貢獻。 | zh_TW |
dc.description.abstract | Neuroblastoma (NB) is an embryonal tumor with various clinical presentations and behaviors. Several genomic alterations has been well-studied in NB, among which genomic amplification of MYCN oncogene, is a strong prognostic biomarker with worsens outcome. Long noncoding RNAs (lncRNAs), constitute major proportion of the cellular transcripts with no coding capacity. One of their function is to guide transcription factors to the target genes and facilitate gene expression. However, relative contribution of lncRNA and MYCN to the advanced NB has remained unclear. Herein, by applying a network-based integrative analysis on MYCN amplified and MYCN nonamplified lncRNA expression profile from both RNA-seq and microarray platform, we identified lncRNA, SNHG1 to be differentially expressed and strongly correlated with MYCN in MYCN-amplified NB. The expression of SNHG1 was validated by RT-qPCR in NB cell lines. Survival analysis revealed that higher expression of SNHG1 significantly associates with poor patient survival. Moreover, knockdown of MYCN in MYCN-amplified NB cell lines inhibited SNHG1 expression. Furthermore, to unravel the role of SNHG1 in NB, we extracted SNHG1-interacting proteins by RNA-protein pull down assay coupled with liquid chromatography-tandem mass spectrometry (LC-MS/MS). We identified 27 SNHG1-interacting proteins in common from three NB cell lines. However, only three SNHG1-interacting proteins, MATR3, YBX1 and HHRNPL have binding site detected by DeepBind motif analysis. Western blot confirms interaction of MATR3 with SNHG1. Additionally, we further validated the direct interaction between MATR3 and SNHG1 by RNA-immunoprecipation (IP). MATR3 is known to be involved in RNA transport and stabilization. Therefore, we proposed that MATR3 after interacting with SNHG1 might help in SNHG1 transcription and stabilization. In conclusion, our study unveils that SNHG1 could be a prognostic marker for high-risk NB and possibly stabilized by MATR3. Our results might provide future directions for the development of therapeutic strategies against high-risk NB. | en |
dc.description.provenance | Made available in DSpace on 2021-06-17T01:42:59Z (GMT). No. of bitstreams: 1 ntu-106-R04b43006-1.pdf: 4498296 bytes, checksum: 0adb54fc9b83a7a584f70067a76eb81b (MD5) Previous issue date: 2017 | en |
dc.description.tableofcontents | 口試委員會審定書 I
致謝 II 中文摘要 III Abstract V Contents VII List of Tables XI List of Figures XII Chapter 1. Introduction 1 1.1 Neuroblastoma 1 1.1.1 Tumor Stage 2 1.2 v-myc avian myelocytomatosis viral oncogene neuroblastoma derived homolog (MYCN) 3 1.3 Gene expression analysis 4 1.4 Long noncoding RNA 5 1.5 Small nucleolar RNA host gene 1 (SNHG1) 6 1.6 Motivation 7 Chapter 2. Materials and Methods 8 2.1 LncRNA expression analysis 8 2.2 Cell culture 8 2.3 RNA extraction and reverse transcription 9 2.4 Real-time quantitative polymerase chain reaction (RT-qPCR) 10 2.5 Transient siRNA knockdown of MYCN and SNHG1 11 2.6 Construction of SP6 promoter regions in SNHG1 12 2.7 In vitro transcription assay 12 2.8 Protein precipitation 13 2.9 RNA-Protein Pull Down assay 14 2.10 Reduction, alkylation and digestion of proteins 16 2.11 ZipTip desalting 17 2.12 NanoLC-MS/MS analysis 18 2.13 Proteome data analysis 19 2.14 Comparison of proteome profile of NB cell lines 20 2.15 Cellular location analysis 20 2.16 Molecular functional enrichment analysis 20 2.17 RNA binding protein recognizing motif analysis 21 2.18 Western blot analysis 21 2.19 The gene correlation analysis and the survival rate 22 2.20 RNA immunoprecipitation 22 2.21 Reverse transcription polymerase chain reaction 23 Chapter 3. Results 24 3.1 MYCN regulated long noncoding RNAs 24 3.2 Validation of expression of the potential lncRNAs in NB cell lines 25 3.3 Knock down of MYCN down regulates SNHG1 expression 25 3.4 ChIP-seq data revealed MYCN binding in the promoter of SNHG1 26 3.5 Identification of proteins interacting with SNHG1 26 3.6 Biological processes and pathways regulated by SNHG1 27 3.7 SNHG1 involved in biological pathways via interaction with various regulators 28 3.8 SNHG1 recognized the regulators via binding motif 28 3.9 MATR3 is associated with SNHG1 29 Chapter 4. Discussion 30 Chapter 5 Conclusion 34 Reference 36 Figures 92 | |
dc.language.iso | en | |
dc.title | 探討長鍊非編碼核糖核酸SNHG1在人類神經母細胞瘤的角色 | zh_TW |
dc.title | Long Non-coding RNA SNHG1 in Neuroblastoma | en |
dc.type | Thesis | |
dc.date.schoolyear | 105-2 | |
dc.description.degree | 碩士 | |
dc.contributor.oralexamcommittee | 黃宣誠,許文明,溫進德,黃敏銓 | |
dc.subject.keyword | 神經母細胞瘤,MYCN,長鏈非編碼核糖核酸,SNHG1,核糖核酸-蛋白質拉下測定實驗,液相層析串聯式質譜儀,Matrin 3, | zh_TW |
dc.subject.keyword | Neuroblastoma,MYCN,Long non-coding RNA,SNHG1,RNA-protein pull down assay,LC-MS/MS,RNA-immunoprecipation (IP),MATR3, | en |
dc.relation.page | 111 | |
dc.identifier.doi | 10.6342/NTU201701980 | |
dc.rights.note | 有償授權 | |
dc.date.accepted | 2017-07-28 | |
dc.contributor.author-college | 生命科學院 | zh_TW |
dc.contributor.author-dept | 分子與細胞生物學研究所 | zh_TW |
顯示於系所單位: | 分子與細胞生物學研究所 |
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