進階搜尋


   電子論文尚未授權公開,紙本請查館藏目錄
(※如查詢不到或館藏狀況顯示「閉架不公開」,表示該本論文不在書庫,無法取用。)
系統識別號 U0026-0908201820004200
論文名稱(中文) miR-196a通過標靶IMP3對神經型態的保護作用
論文名稱(英文) The Neuroprotective Effect of miR-196a on Neuronal Morphology through Targeting IMP3
校院名稱 成功大學
系所名稱(中) 生理學研究所
系所名稱(英) Department of Physiology
學年度 106
學期 2
出版年 107
研究生(中文) 楊涵茵
研究生(英文) Han-In Yang
學號 S36054075
學位類別 碩士
語文別 英文
論文頁數 90頁
口試委員 指導教授-楊尚訓
口試委員-曾淑芬
口試委員-邱文泰
中文關鍵字 亨丁頓式舞蹈症  微核醣核酸196a  神經型態  IMP3 
英文關鍵字 Huntington’s disease (HD)  miR-196a  neuronal morphology  IMP3 
學科別分類
中文摘要 亨丁頓式舞蹈症 (Huntington’s disease) 為一遺傳性神經退化疾病,伴隨變異的基因表現,其主對中樞系統產生神經毒性,造成個體的運動控制失調及認知功能障礙。先前實驗室的研究發現,過量表達微核醣核酸196a (miR-196a) 使亨丁頓式舞蹈症在細胞與動物疾病模式的病徵減輕,並為神經骨架蛋白提供有益的調節。在當前的研究中,我們致力於闡發miR-196a在神經退化中保護神經型態所透過的深入途徑。根據生物資訊工具的預測,一個參與癌細胞惡性轉移時細胞骨架重塑的分子,胰島素樣生長因子2 mRNA結合蛋白3 (insulin-like growth factor 2 mRNA-binding protein 3; Igf2bp3 or IMP3) 被視為是miR-196a 潛在的標靶基因,因此我們推測在亨丁頓式舞蹈症中,miR-196a可能抑制IMP3而改善神經的型態。本研究中證實miR-196a藉由結合在IMP3 mRNA的三端不轉譯區 (3’UTR) 而抑制IMP3在神經母細胞瘤-2a (N2a) 中的表現,此外在 miR-196a的基因轉殖小鼠中,內源性的IMP3表達亦受到限制。我們進一步在經視黃酸 (retinoic acid) 分化的N2a神經細胞及初代培養之小鼠大腦皮質神經元中呈現miR-196a促進神經軸突生長及其對IMP3的抑制效果,而過量表達IMP3則阻斷miR-196a對神經型態的保護作用。同時,外源性的IMP3限制了神經軸突生長並導致不正常的神經型態,包含纖維型的微絲蛋白 (F-actin) 表現降低以及細胞形狀較扁。再者,在亨丁頓式舞蹈症疾病模式的R6/2小鼠中,我們發現IMP3蛋白在成體大腦皮質的異位表達,且該表現量與疾病進程相關。此研究結果顯示提升的IMP3表現量在神經型態上扮演著有害的角色,而miR-196a可透過抑制IMP3以助於神經發展。了解miR-196a保護神經的機制並提供疾病相關之標的蛋白將對未來神經退化的基因治療帶來新面向。
英文摘要 Huntington’s disease (HD) is an inherited neurodegenerative disease leading to motor control dysfunction and cognitive deficit in patients, resulting from the neurotoxicity primarily in the central nervous system (CNS) along with altered gene expression. Previously, our research had found that overexpression of miR-196a ameliorated pathological phenotypes of HD models in vitro and in vivo and provided beneficial regulations for neuronal cytoskeleton. We now elucidate the mechanism of the neuroprotective effects of miR-196a. Bioinformatics predicts that insulin-like growth factor 2 mRNA-binding protein 3 (IGF2BP3 or IMP3) is a potential target gene of miR-196a, which is involved in cytoskeleton remodeling during malignant transformation in cancers. Therefore, we hypothesize that miR-196a may improve the neuronal morphology through targeting IMP3. Here, we confirm that miR-196a inhibits the endogenous expression level of IMP3 in N2a cells by targeting the 3’UTR of IMP3 transcript. Besides, the endogenous IMP3 is suppressed in miR-196a transgenic mice. We further show that miR-196a inhibits IMP3 in N2a cells differentiated by retinoic acid and in mouse primary cortical neurons, and overexpression of IMP3 blocks the morphology protective effect of miR-196a. Additionally, the exogenous IMP3 restrains the neurite outgrowth and leads to abnormal morphology, including decreased F-actin intensity and flattened cell shape. Furthermore, in screening the expression profiling of IMP3 in the R6/2 HD mouse model, we find an ectopic expression pattern of IMP3 in their adult cortical tissues, which is distinct from the wild type mice and correlated with disease progression. These results implicate a detrimental role of elevated IMP3 in neuronal pathogenesis, and miR-196a may provide beneficial effects for neuronal morphology through targeting IMP3. In future work, we will study the role of IMP3 in the neuroprotective effect of miR-196a in HD models in vitro and in vivo. We anticipate that this study will shed light on promising treatment strategies for HD.
論文目次 Contents
Abstract...I
中文摘要...II
Acknowledgements...III
Contents...IV
Figure Contents...VII
Chapter 1. Introduction...1
1-1. Neuronal morphology...1
1-2. Neuronal cytoskeleton...2
1-3. Actin filaments and neurite outgrowth...4
1-4. Background of miRNA...5
1-5. miRNA applications...6
1-6. Background of IMP3...7
1-7. Potential roles of IMP3...8
Chapter 2. Objectives...11
2-1. Research rationales...11
2-2. Specific aims...12
Chapter 3. Materials and Methods...13
3-1. DNA construction...13
3-2. DNA transformation...13
3-3. Plasmid extraction...14
3-4. N2a cell culture and differentiation...15
3-5. Cell freezing and thawing...16
3-6. Transfection...17
3-7. Luciferase/β-gal Reporter assay...17
3-8. miRNA transfection...19
3-9. Ubi-IMP3-flag overexpression...19
3-10. Neurite outgrowth of N2a cells...19
3-11. Primary culture of cortical neurons...20
3-12. Western blot...22
3-13. Immunofluorescent staining...25
3-14. Imaging and analysis...27
(1) Imaging setting...27
(2) Analysis of neuronal morphology...29
(3) Analysis of the fluorescence intensity...30
(4) Analysis of the nucleus circularity...31
3-15. Statistical analysis...31
Chapter 4. Results...32
Aim 1. To identify IMP3 as a target gene of miR-196a....32
4-1. The inhibitory effect of miR-196a on IMP3 in vitro and in vivo...32
Aim 2. To investigate whether miR-196a improves neuronal morphology by targeting IMP3....33
4-2. The protective effect of miR-196a on neuronal morphology by suppressing IMP3...34
Aim 3. To investigate the role of IMP3 in neuronal morphology...36
4-3. The detrimental role of IMP3 on neuronal morphology... 36
4-4. The blockage of the protective effect of miR-196a on neuronal morphology by overexpressing IMP3...38
Chapter 5. Discussion...39
5-1. New findings in this thesis...39
5-2. The suppression of IMP3 by miR-196a in brain...39
(1) Contribution to neuronal morphology...39
(2) Potential impact in adult brains...40
5-3. The potential impact of IMP3 on neuronal morphology... 41
5-4. Research limitations...42
5-5. Future work...43
(1) The downstream regulation of IMP3 in neuronal morphology...43
(2) The ectopic expression of IMP3 in adult cortical tissues in R6/2 mice...44
Chapter 6. Conclusion...46
Chapter 7. References...47
Chapter 8. Figures...58

Figure Contents
Figure 1. miR-196a directly targets 3’-UTR of IMP3 in N2a cells....59
Figure 2. miR-196a inhibits the protein expression of IMP3 in N2a cells....60
Figure 3. The expression level of endogenous IMP3 is suppressed in miR-196a-transgenic mice....61
Figure 4. miR-196a inhibits the protein expression of IMP3 in RA-differentiated N2a cells....64
Figure 5. miR-196a suppresses the expression level of IMP3 and enhances neurite outgrowth in RA-differentiated N2a cells....67
Figure 6. miR-196a suppresses the expression level of IMP3 and enhances neurite outgrowth in primary cortical neurons....71
Figure 7. IMP3 is overexpressed by the Ubi-IMP3-flag construct....74
Figure 8. Overexpressing IMP3 leads to worsen neuronal morphology and decreased intensity of phalloidin in RA-differentiated N2a cells....78
Figure 9. Overexpressing IMP3 leads to worsen neurite outgrowth in primary cortical neurons....82
Figure 10. miR-196a improves neuronal morphology by targeting IMP3....86
Figure 11. An RNA-seq of IMP3-bound RNA is enriched in the cytoskeleton remodeling pathway....88
Figure 12. IMP3 is abnormally expressed in the adult cortical tissue of R6/2 HD mice....90
參考文獻 1. Craig A. M. and Banker G., Neuronal polarity. Annual Review of Neuroscience, 1994. 17: p. 267-310.
2. Sanford L., Palay, et al., The axon hillock and the initial segment. The Journal of Cell Biology, 1968. 38: p. 191-201.
3. Hull C., Adesnik H., and Scanziani M., Neocortical disynaptic inhibition requires somatodendritic integration in interneurons. Journal of Neuroscience, 2009. 29(28): p. 8991-5.
4. van Kesteren, R. E. and Spencer G. E., The role of neurotransmitters in neurite outgrowth and synapse formation. Reviews in the Neurosciences, 2003. 14(3): p. 217-31.
5. Bulloch A. G. M. and Kater S. B., Neurite outgrowth and selection of new electrical connections by adult helisoma neurons. Journal of Neurophysiology, 1982. 48(2): p. 569-82.
6. Ganguly A., et al., A dynamic formin-dependent deep F-actin network in axons. Journal of Cell Biology, 2015. 210(3): p. 401-17.
7. Eira J., et al., The cytoskeleton as a novel therapeutic target for old neurodegenerative disorders. Progress in Neurobiology, 2016. 141: p. 61-82.
8. Poulain F.E. and Sobel A., The microtubule network and neuronal morphogenesis: dynamic and coordinated orchestration through multiple players. Molecular and Cellular Neuroscience, 2010. 43(1): p. 15-32.
9. Caceres A., Ye B., and Dotti C.G., Neuronal polarity: demarcation, growth and commitment. Current Opinion in Cell Biology, 2012. 24(4): p. 547-53.
10. Dent E. W. and Gertler F. B., Cytoskeletal dynamics and transport in growth cone motility and axon guidance. Neuron, 2003. 40(2): p. 209-27.
11. Lowery L.A. and van Vactor D., The trip of the tip: understanding the growth cone machinery. Nature Reviews Molecular Cell Biology, 2009. 10(5): p. 332-43.
12. Olah J., et al., Interactions of pathological hallmark proteins: tubulin polymerization promoting protein/p25, beta-amyloid, and alpha-synuclein. The Journal of Biological Chemistry, 2011. 286(39): p. 34088-100.
13. Song M. S., Saavedra L., and de Chaves E. I., Apoptosis is secondary to non-apoptotic axonal degeneration in neurons exposed to Abeta in distal axons. Neurobiology of Aging, 2006. 27(9): p. 1224-38.
14. Munch G., et al., Microglial activation induces cell death, inhibits neurite outgrowth and causes neurite retraction of differentiated neuroblastoma cells. Experimental Brain Research, 2003. 150(1): p. 1-8.
15. Hoffner G., Kahlem P., and Djian P., Perinuclear localization of huntingtin as a consequence of its binding to microtubules through an interaction with beta-tubulin relevance to Huntington's disease. Journal of Cell Science, 2002. 115(5): p. 941-8.
16. Looi J. C. and Walterfang M., Striatal morphology as a biomarker in neurodegenerative disease. Molecular Psychiatry, 2013. 18(4): p. 417-24.
17. Nagy J., et al., Altered neurite morphology and cholinergic function of induced pluripotent stem cell-derived neurons from a patient with Kleefstra syndrome and autism. Translational Psychiatry, 2017. 7(7): p. e1179.
18. Fletcher D. A. and Mullins R. D., Cell mechanics and the cytoskeleton. Nature, 2010. 463(7280): p. 485-92.
19. Peng J. M., et al., Actin cytoskeleton remodeling drives epithelial‐mesenchymal transition for hepatoma invasion and metastasis in mice. Hepatology, 2018. 67(6): p. 2226-43.
20. Lopez-Posadas R., et al., Interplay of GTPases and cytoskeleton in cellular barrier defects during gut inflammation. Frontiers in Immunology, 2017. 8: p. 1240.
21. Nicolas A., et al., Genome-wide analyses identify KIF5A as a novel ALS gene. Neuron, 2018. 97(6): p. 1268-83.
22. Kapitein L. C. and Hoogenraad C. C., Building the Neuronal Microtubule Cytoskeleton. Neuron, 2015. 87(3): p. 492-506.
23. Luo L., Actin cytoskeleton regulation in neuronal morphogenesis and structural plasticity. Annual Review of Cell and Developmental Biology, 2002. 18: p. 601-35.
24. Spudich J. A., Huxley H. E., and Finch J. T., Regulation of skeletal muscle contraction II. Structural studies of the interaction of the tropomyosin-troponin complex with actin. Journal of Molecular Biology, 1972. 72(3): p. 619-32.
25. Mitchison T. and Kirchner M., Dynamic instability of microtubule growth. Nature, 1984. 312: p. 237-42.
26. Uchida A., et al., Severing and end-to-end annealing of neurofilaments in neurons. PNAS, 2013. 110(29): e2696-705.
27. Kapitein L. C. and Hoogenraad C. C., Which way to go? Cytoskeletal organization and polarized transport in neurons. Molecular and Cellular Neuroscience, 2011. 46(1): p. 9-20.
28. de Forges H., Bouissou A., and Perez F., Interplay between microtubule dynamics and intracellular organization. The International Journal of Biochemistry and Cell Biology, 2012. 44(2): p. 266-74.
29. Vale R. D., The molecular motor toolbox for intracellular transport. Cell, 2003. 112(4): p. 467-80.
30. Pardee J. D., Spudich J. A., Mechanism of K+-induced actin assembly. Journal of Cell Biology, 1982. 93(3): p. 648-54.
31. Pollard T. D. and Mooseker M. S., Direct measurement of actin polymerization rate constants by electron microscopy of actin filaments nucleated by isolated microvillus cores. Journal of Cell Biology, 1981. 88(3): p. 654-9.
32. Vignjevic D., et al., Formation of filopodia-like bundles in vitro from a dendritic network. Journal of Cell Biology, 2003. 160(6): p. 951-62.
33. Davidson A. J. and Wood W., Unravelling the actin cytoskeleton: a new competitive edge?. Trends in Cell Biology, 2016. 26(8): p. 569-76.
34. Tanaka E. M., and Kirschner M. W., Microtubule behavior in the growth cones of living neurons during axon elongation. Journal of Cell Biology, 1991. 115(2): p. 345–63.
35. Wu C. L., Interplay between cell migration and neurite outgrowth determines SH2B1β-enhanced neurite regeneration of differentiated PC12 cells. PLoS One, 2012. 7(4): e34999.
36. Schaefer A.W., et al., Coordination of actin filament and microtubule dynamics during neurite outgrowth. Developmental Cell , 2008. 15(1): p. 146-62.
37. Mattila P. K. and Lappalainen P., Filopodia: molecular architecture and cellular functions. Nature Reviews Molecular Cell Biology, 2008. 9(6): p. 446-54.
38. Pollard T. D and Borisy G. G., Cellular motility driven by assembly and disassembly of actin filaments. Cell, 2003. 112(4): p. 453-65.
39. Chhabra E. S., Higgs H. N., The many faces of actin matching assembly factors with cellular structures. Nature Cell Biology, 2007. 9(10): p. 1110-21.
40. Bentley A and Toroian-Raymond A., Disoriented pathfinding by pioneer neurone growth cones deprived of filopodia by cytochalasin treatment. Nature, 1986. 323: p. 712-5.
41. Challacombe J. F., Snow D. M., and Letourneau P. C., Dynamic microtubule ends are required for growth cone turning to avoid an inhibitory guidance cue. The Journal of Neuroscience, 1997. 17(9): p. 3085-95.
42. Svitkina T. M., et al., Mechanism of filopodia initiation by reorganization of a dendritic network. Journal of Cell Biology, 2003. 160(3): p. 409-21.
43. Zhang S. X., et al., Actin aggregations mark the stes of neurite initiation. Neuroscience Bulletin, 2016. 32(1): p. 1-15.
44. Chia J. X., Efimova N., and Svitkina T.M., Neurite outgrowth is driven by actin polymerization even in the presence of actin polymerization inhibitors. Molecular Biology of the Cell, 2016. 27(23): p. 3695-704.
45. Lavut A. and Raveh D., Sequestration of highly expressed mRNAs in cytoplasmic granules, P-bodies, and stress granules enhances cell viability. PLoS Genetics, 2012. 8(2): p. e1002527.
46. Yekta S., Shih I. H., and Bartel D. P., MicroRNA-directed cleavage of HoxB8 mRNA. Science, 2004. 304(5670): p. 594-6.
47. Bartel D. P., MicroRNAs genomics, biogenesis, mechanism, and function. Cell, 2004. 116(2): p. 281-97.
48. Lee Y., et al., MicroRNA genes are transcribed by RNA polymerase II. The EMBO Journal, 2004. 23(20): p. 4051-60.
49. Doerks T., et al., Systematic identification of novel protein domain families associated with nuclear functions. Genome Research, 2002. 12(1): p. 47-56.
50. Melamed Z., et al., Alternative splicing regulates biogenesis of miRNAs located across exon-intron junctions. Molecular Cell, 2013. 50(6): p. 869-81.
51. Lee Y. MicroRNA maturation stepwise processing and subcellular localization. The EMBO Journal, 2002. 21(17): p. 4663-70.
52. Yi R., et al., Exportin-5 mediates the nuclear export of pre-microRNAs and short hairpin RNAs. Genes and Development, 2003. 17(24): p. 3011-6.
53. Bohnsack M. T., Exportin 5 is a RanGTP-dependent dsRNA-binding protein that mediates nuclear export of pre-miRNAs. RNA, 2004. 10(2): p. 185-91.
54. Lund E., Nuclear export of microRNA precursors. Science, 2004. 303(5654): p. 95-8.
55. Winter J., Many roads to maturity microRNA biogenesis pathways and their regulation. NatureCell Biology, 2009. 11(3): p. 228-34.
56. Salomon W. E., et al., Single-molecule imaging reveals that argonaute reshapes the binding properties of its nucleic acid guides. Cell, 2015. 162(1): p. 84-95.
57. Mansfield J. H., et al., MicroRNA-responsive 'sensor' transgenes uncover Hox-like and other developmentally regulated patterns of vertebrate microRNA expression. Nature Genetics, 2004. 36(10): p. 1079-83.
58. McNeill E. and Van Vactor D., MicroRNAs shape the neuronal landscape. Neuron, 2012. 75(3): p. 363-79.
59. Londin E., et al., Analysis of 13 cell types reveals evidence for the expression of numerous novel primate- and tissue-specific microRNAs. PNAS, 2015. 112(10): e1106-15.
60. Miller F. D. and Gauthier A. S., Timing is everything: making neurons versus glia in the developing cortex. Neuron, 2007. 54(3): p. 357-69.
61. Hazra B., Kumawat K. L., and Basu A., The host microRNA miR-301a blocks the IRF1-mediated neuronal innate immune response to Japanese encephalitis virus infection. Science Signaling, 2017. 10: e5185.
62. Akerblo, M., et al., microRNA-125 distinguishes developmentally generated and adult-born olfactory bulb interneurons. Development, 2014. 141(7): p. 1580-8.
63. Edbauer D., et al., Regulation of synaptic structure and function by FMRP-associated microRNAs miR-125b and miR-132. Neuron, 2010. 65(3): p. 373-84.
64. Malmevik J., et al., Identification of the miRNA targetome in hippocampal neurons using RIP-seq. Scientific Reports, 2015. 5: p. 12609.
65. Hoefert J. E., et al., The microRNA-200 family coordinately regulates cell adhesion and proliferation in hair morphogenesis. Journal of Cell Biology, 2018. 217(6): p. 2185-204.
66. Chan A.W. and Kocerha J., The Path to microRNA therapeutics in psychiatric and neurodegenerative disorders. Frontiers in Genetics, 2012. 3: p. 82.
67. Cheng P. H., et al., miR-196a ameliorates phenotypes of Huntington disease in cell, transgenic mouse, and induced pluripotent stem cell models. American Journal of Human Genetics, 2013. 93(2): p. 306-12.
68. Yu D., et al., Single-stranded RNAs use RNAi to potently and allele-selectively inhibit mutant huntingtin expression. Cell, 2012. 150(5): p. 895-908.
69. Hong J., et al., MicroRNA function is required for neurite outgrowth of mature neurons in the mouse postnatal cerebral cortex. Frontiers in Cellular Neuroscience, 2013. 7: p. 151.
70. Wang B. and Bao L., Axonal microRNAs: localization, function and regulatory mechanism during axon development. Journal of Molecular Cell Biology, 2017. 9(2): p. 82-90.
71. Smrt R. D., et al., MicroRNA miR-137 regulates neuronal maturation by targeting ubiquitin ligase mind bomb-1. Stem Cells, 2010. 28(6): p. 1060-70.
72. Dajas-Bailador F., et al., microRNA-9 regulates axon extension and branching by targeting Map1b in mouse cortical neurons. Nature Neuroscience, 2012. 15: p. 697-9.
73. Siegel G., et al., A functional screen implicates microRNA-138-dependent regulation of the depalmitoylation enzyme APT1 in dendritic spine morphogenesis. Nature Cell Biology, 2009. 11(6): p. 705-16.
74. Fukuoka M., et al., Supplemental treatment for Huntington's disease with miR-132 that Is deficient in Huntington's disease brain. Molecular Therapy Nucleic Acids, 2018. 11: p. 79-90.
75. Fu M. H., et al., The Potential Regulatory Mechanisms of miR-196a in Huntington's Disease through Bioinformatic Analyses. PLoS One, 2015. 10(9): p. e0137637.
76. Her L. S., et al., miR-196a enhances neuronal morphology through suppressing RANBP10 to provide neuroprotection in Huntington's disease. Theranostics, 2017. 7(9): p. 2452-62.
77. Farina K. L., et al., Two ZBP1 KH domains facilitate beta-actin mRNA localization, granule formation, and cytoskeletal attachment. Journal of Cell Biology, 2003. 160(1): p. 77-87.
78. Chao J. A., et al., ZBP1 recognition of beta-actin zipcode induces RNA looping. Genes and Development, 2010. 24(2): p. 148-58.
79. Lederer M., et al., The role of the oncofetal IGF2 mRNA-binding protein 3 (IGF2BP3) in cancer. Seminars in Cancer Biology, 2014. 29: p. 3-12.
80. Jeng Y. M., et al., Prognostic significance of insulin-like growth factor II mRNA-binding protein 3 expression in gastric adenocarcinoma. British Journal of Surgery, 2009. 96(1): p. 66-73.
81. Schaeffer D. F., et al., Insulin-like growth factor 2 mRNA binding protein 3 (IGF2BP3) overexpression in pancreatic ductal adenocarcinoma correlates with poor survival. BMC Cancer, 2010. 10: p. 59.
82. Jeng Y. M., et al., RNA-binding protein insulin-like growth factor II mRNA-binding protein 3 expression promotes tumor invasion and predicts early recurrence and poor prognosis in hepatocellular carcinoma. Hepatology, 2008. 48(4): p. 1118-27.
83. Kobel M., et al., IGF2BP3 (IMP3) expression is a marker of unfavorable prognosis in ovarian carcinoma of clear cell subtype. Modern Pathology, 2009. 22(3): p. 469-75.
84. Slosar M., et al., Insulin-Like Growth Factor mRNA Binding Protein 3 (IMP3) is Differentially Expressed in Benign and Malignant Follicular Patterned Thyroid Tumors. Endocrine Pathology, 2009. 20(3): p. 149-57.
85. King R. L., et al., IMP-3 is differentially expressed in normal and neoplastic lymphoid tissue. Human Pathology, 2009. 40(12): p. 1699-705.
86. Jiang Z., et al., Analysis of RNA-binding protein IMP3 to predict metastasis and prognosis of renal-cell carcinoma: a retrospective study. The Lancet Oncology, 2006. 7(7): p. 556-4.
87. Findeis-Hosey J. J., et al., IMP3 expression is correlated with histologic grade of lung adenocarcinoma. Hum Pathol, 2010. 41(4): p. 477-84.
88. Walter O., et al., IMP3 is a novel biomarker for triple negative invasive mammary carcinoma associated with a more aggressive phenotype. Human Pathology, 2009. 40(11): p. 1528-33.
89. Hao S., et al., The oncofetal protein IMP3 a novel molecular marker to predict aggressive meningioma. Archives of Pathology and Laboratory Medicine, 2011. 135(8): p. 1032-6.
90. Bell J. L., et al., Insulin-like growth factor 2 mRNA-binding proteins (IGF2BPs): post-transcriptional drivers of cancer progression? Cellular and Molecular Life Sciences, 2013. 70(15): p. 2657-75.
91. Elisha Z., Vg1 RNA binding protein mediates the association of Vg1 RNA with microtubules in Xenopus oocytes. The EMBO Journal, 1995. 14(20): p. 5109-14.
92. Toledano H., et al., The let-7-Imp axis regulates ageing of the Drosophila testis stem-cell niche. Nature, 2012. 485(7400): p. 605-10.
93. Boylan K. L. M., et al., A motility screen identifies Drosophila IGF-II mRNA-binding protein, a zipcode-binding protein that functions in oogenesis and synaptogenesis. PLoS Genetics, 2005. p. e36.
94. Hafner M., et al., Transcriptome-wide identification of RNA-binding protein and microRNA target sites by PAR-CLIP. Cell, 2010. 141(1): p. 129-41.
95. Mizutani R., et al., Oncofetal protein IGF2BP3 facilitates the activity of proto-oncogene protein eIF4E through the destabilization of EIF4E-BP2 mRNA. Oncogene, 2016. 35(27): p. 3495-502.
96. Zhou Y., et al., IGF2BP3 functions as a potential oncogene and is a crucial target of miR-34a in gastric carcinogenesis. Molecular Cancer, 2017. 16(1): p. 77.
97. Palanichamy J. K., et al., RNA-binding protein IGF2BP3 targeting of oncogenic transcripts promotes hematopoietic progenitor proliferation. Journal of Clinical Investigation, 2016. 126(4): p. 1495-511.
98. Ennajdaoui H., et al., IGF2BP3 Modulates the Interaction of Invasion-Associated Transcripts with RISC. Cell Reports, 2016. 15(9): p. 1876-83.
99. Vikesaa J., et al., RNA-binding IMPs promote cell adhesion and invadopodia formation. The EMBO Journal, 2006. 25(7): p. 1456-68.
100. Vikesaa J., Neonatal expression of RNA-binding protein igf2bp3 regulates the human fetal-adult megakaryocyte transition. The EMBO Journal. 25(7): 1456-68.
101. Nielsen J., et al., Sequential dimerization of human zipcode-binding protein IMP1 on RNA: a cooperative mechanism providing RNP stability. Nucleic Acids Research, 2004. 32(14): p. 4368-76.
102. Li W., et al., Role of IGF2BP3 in trophoblast cell invasion and migration. Cell Death and Disease, 2014. 5: p. e1025.
103. Jonson L., et al., IMP3 RNP safe houses prevent miRNA-directed HMGA2 mRNA decay in cancer and development. Cell Reports, 2014. 7(2): p. 539-51.
104. Gutschner T., et al., Insulin-like growth factor 2 mRNA-binding protein 1 (IGF2BP1) is an important protumorigenic factor in hepatocellular carcinoma. Hepatology, 2014. 59(5): p. 1900-11.
105. Pan F., et al., ZBP2 facilitates binding of ZBP1 to beta-actin mRNA during transcription. Molecular and Cellular Biology, 2007. 27(23): p. 8340-51.
106. Batista A. F. and Hengst U., Intra-axonal protein synthesis in development and beyond. International Journal of Developmental Neuroscience, 2016. 55: p. 140-9.
107. Tasdemir-Yilmaz O. E. and Segal R. A., There and back again: coordinated transcription, translation and transport in axonal survival and regeneration. Current Opinion in Neurobiology, 2016. 39: p. 62-8.
108. Hoss A. G., et al., MicroRNAs located in the Hox gene clusters are implicated in huntington's disease pathogenesis. PLoS Genetics, 2014. 10(2): p. e1004188.
109. Walker F. O., Huntington's disease. The Lancet, 2007. 369(9557): p. 218-28.
110. Taniuchi K., et al., IGF2BP3-mediated translation in cell protrusions promotes cell invasiveness and metastasis of pancreatic cancer. Oncotarget, 2014. 5(16): p. 6832-45.
111. Lin C. H., Hsieh M., and Fan S.S., The promotion of neurite formation in Neuro2A cells by mouse Mob2 protein. FEBS Lett, 2011. 585(3): p. 523-30.
112. Kommaddi R. P., et al., Abeta mediates F-actin disassembly in dendritic spines leading to cognitive deficits in Alzheimer's disease. Journal of Neuroscience, 2018. 38(5): p. 1085-99.
113. Nielsen F. C., Nielsen J, and Christiansen J., A family of IGF-II mRNA binding proteins (IMP) involved in RNA trafficking. Scandinavian Journal of Clinical and Laboratory Investigation, 2009. 61(234): p. 93-9.
Hammer N. A., et al., Expression of IGF-II mRNA-binding proteins (IMPs) in gonads and testicular cancer. Reproduction, 2005. 130(2): p. 203-12.
114. Nielsen J., et al., A family of insulin-like growth factor II mRNA-binding proteins represses translation in late development. Molecular of Cell Biology, 1999.19(2): p. 1262-70.
115. von Schimmelmann M., et al., Polycomb repressive complex 2 (PRC2) silences genes responsible for neurodegeneration. Nature Neuroscience, 2016. 19(10): p. 1321-30.
116. Chen S.T., et al., Insulin-like growth factor II mRNA-binding protein 3 expression predicts unfavorable prognosis in patients with neuroblastoma. Cancer Science, 2011. 102(12): p. 2191-8.
117. Mancarella C., et al., Insulin-Like Growth Factor 2 mRNA-Binding Protein 3 Influences Sensitivity to Anti-IGF System Agents Through the Translational Regulation of IGF1R. Frontiers in Endocrinology, 2018. 9: p. 178.
118. Reis S. A., et al., Striatal neurons expressing full-length mutant huntingtin exhibit decreased N-cadherin and altered neuritogenesis. Human Molecular Genetics, 2011. 20(12): p. 2344-55.
119. Hsieh P.C., et al., DDA3 stabilizes microtubules and suppresses neurite formation. Journal of Cell Science, 2012. 125: p. 3402-11.
120. Hsieh P. C., Cofilin phosphorylation by LIM-kinase 1 and its role in Rac-mediated actin reorganization. Journal of Cell Science, 2012. 125: p. 3402-341.
121. Hou M., et al., SEPT7 overexpression inhibits glioma cell migration by targeting the actin cytoskeleton pathway. Oncology Reports, 2016. 35(4): p. 2003-10.
122. Lee J. M., et al., Unbiased Gene Expression Analysis Implicates the huntingtin Polyglutamine Tract in Extra-mitochondrial Energy Metabolism. PLoS Genetics, 2007. 3(8): e135.
論文全文使用權限
  • 同意授權校內瀏覽/列印電子全文服務,於2023-07-30起公開。
  • 同意授權校外瀏覽/列印電子全文服務,於2023-07-30起公開。


  • 如您有疑問,請聯絡圖書館
    聯絡電話:(06)2757575#65773
    聯絡E-mail:etds@email.ncku.edu.tw