請用此 Handle URI 來引用此文件：
http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/55588完整後設資料紀錄
| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 陳俊宏(Chun-Hong Chen) | |
| dc.contributor.author | Chao-Yi Chen | en |
| dc.contributor.author | 陳昭儀 | zh_TW |
| dc.date.accessioned | 2021-06-16T04:11:06Z | - |
| dc.date.available | 2017-11-14 | |
| dc.date.copyright | 2014-11-14 | |
| dc.date.issued | 2014 | |
| dc.date.submitted | 2014-08-20 | |
| dc.identifier.citation | Alvarez-Garcia, I., and Miska, E.A. (2005). MicroRNA functions in animal development and human disease. Development 132, 4653-4662.
Ambros, V. (2001). microRNAs: tiny regulators with great potential. Cell 107, 823-826. Aravin, A.A., Lagos-Quintana, M., Yalcin, A., Zavolan, M., Marks, D., Snyder, B., Gaasterland, T., Meyer, J., and Tuschl, T. (2003). The small RNA profile during Drosophila melanogaster development. Developmental cell 5, 337-350. Avruch, J., Long, X., Ortiz-Vega, S., Rapley, J., Papageorgiou, A., and Dai, N. (2009). Amino acid regulation of TOR complex 1. American journal of physiology Endocrinology and metabolism 296, E592-602. Baltzer, C., Tiefenbock, S.K., Marti, M., and Frei, C. (2009). Nutrition controls mitochondrial biogenesis in the Drosophila adipose tissue through Delg and cyclin D/Cdk4. PloS one 4, e6935. Bartel, D.P. (2004). MicroRNAs: genomics, biogenesis, mechanism, and function. Cell 116, 281-297. Bergmann, A., Agapite, J., McCall, K., and Steller, H. (1998). The Drosophila gene hid is a direct molecular target of Ras-dependent survival signaling. Cell 95, 331-341. Bilak, A., and Su, T.T. (2009). Regulation of Drosophila melanogaster pro-apoptotic gene hid. Apoptosis : an international journal on programmed cell death 14, 943-949. Boehm, M., and Slack, F. (2005). A developmental timing microRNA and its target regulate life span in C. elegans. Science 310, 1954-1957. Borchert, G.M., Lanier, W., and Davidson, B.L. (2006). RNA polymerase III transcribes human microRNAs. Nature structural & molecular biology 13, 1097-1101. Boya, P., Gonzalez-Polo, R.A., Casares, N., Perfettini, J.L., Dessen, P., Larochette, N., Metivier, D., Meley, D., Souquere, S., Yoshimori, T., et al. (2005). Inhibition of macroautophagy triggers apoptosis. Molecular and cellular biology 25, 1025-1040. Brennecke, J., Hipfner, D.R., Stark, A., Russell, R.B., and Cohen, S.M. (2003). bantam encodes a developmentally regulated microRNA that controls cell proliferation and regulates the proapoptotic gene hid in Drosophila. Cell 113, 25-36. Cagan, R.L., and Ready, D.F. (1989). The emergence of order in the Drosophila pupal retina. Developmental biology 136, 346-362. Cashio, P., Lee, T.V., and Bergmann, A. (2005). Genetic control of programmed cell death in Drosophila melanogaster. Seminars in cell & developmental biology 16, 225-235. Chen, P., Nordstrom, W., Gish, B., and Abrams, J.M. (1996). grim, a novel cell death gene in Drosophila. Genes & development 10, 1773-1782. Chen, P., Rodriguez, A., Erskine, R., Thach, T., and Abrams, J.M. (1998). Dredd, a novel effector of the apoptosis activators reaper, grim, and hid in Drosophila. Developmental biology 201, 202-216. Codogno, P., and Meijer, A.J. (2005). Autophagy and signaling: their role in cell survival and cell death. Cell death and differentiation 12 Suppl 2, 1509-1518. Doench, J.G., Petersen, C.P., and Sharp, P.A. (2003). siRNAs can function as miRNAs. Genes & development 17, 438-442. Domingues, C., and Ryoo, H.D. (2012). Drosophila BRUCE inhibits apoptosis through non-lysine ubiquitination of the IAP-antagonist REAPER. Cell death and differentiation 19, 470-477. Dorstyn, L., Colussi, P.A., Quinn, L.M., Richardson, H., and Kumar, S. (1999a). DRONC, an ecdysone-inducible Drosophila caspase. Proceedings of the National Academy of Sciences of the United States of America 96, 4307-4312. Dorstyn, L., Read, S.H., Quinn, L.M., Richardson, H., and Kumar, S. (1999b). DECAY, a novel Drosophila caspase related to mammalian caspase-3 and caspase-7. The Journal of biological chemistry 274, 30778-30783. Doumanis, J., Quinn, L., Richardson, H., and Kumar, S. (2001). STRICA, a novel Drosophila melanogaster caspase with an unusual serine/threonine-rich prodomain, interacts with DIAP1 and DIAP2. Cell death and differentiation 8, 387-394. Edgar, B.A. (2006). From cell structure to transcription: Hippo forges a new path. Cell 124, 267-273. Esquela-Kerscher, A., and Slack, F.J. (2006). Oncomirs - microRNAs with a role in cancer. Nature reviews Cancer 6, 259-269. Esslinger, S.M., Schwalb, B., Helfer, S., Michalik, K.M., Witte, H., Maier, K.C., Martin, D., Michalke, B., Tresch, A., Cramer, P., et al. (2013). Drosophila miR-277 controls branched-chain amino acid catabolism and affects lifespan. RNA biology 10, 1042-1056. Fan, Y., Lee, T.V., Xu, D., Chen, Z., Lamblin, A.F., Steller, H., and Bergmann, A. (2010). Dual roles of Drosophila p53 in cell death and cell differentiation. Cell death and differentiation 17, 912-921. Fraser, A.G., and Evan, G.I. (1997). Identification of a Drosophila melanogaster ICE/CED-3-related protease, drICE. The EMBO journal 16, 2805-2813. Fuchs, Y., and Steller, H. (2011). Programmed cell death in animal development and disease. Cell 147, 742-758. Genevet, A., and Tapon, N. (2011). The Hippo pathway and apico-basal cell polarity. The Biochemical journal 436, 213-224. Giannakou, M.E., and Partridge, L. (2007). Role of insulin-like signalling in Drosophila lifespan. Trends in biochemical sciences 32, 180-188. Gregory, R.I., Chendrimada, T.P., Cooch, N., and Shiekhattar, R. (2005). Human RISC couples microRNA biogenesis and posttranscriptional gene silencing. Cell 123, 631-640. Grether, M.E., Abrams, J.M., Agapite, J., White, K., and Steller, H. (1995). The head involution defective gene of Drosophila melanogaster functions in programmed cell death. Genes & development 9, 1694-1708. Hagiwara, A., Nishiyama, M., and Ishizaki, S. (2012). Branched-chain amino acids prevent insulin-induced hepatic tumor cell proliferation by inducing apoptosis through mTORC1 and mTORC2-dependent mechanisms. Journal of cellular physiology 227, 2097-2105. Halder, G., and Johnson, R.L. (2011). Hippo signaling: growth control and beyond. Development 138, 9-22. Hammond, S.M. (2006). MicroRNA therapeutics: a new niche for antisense nucleic acids. Trends in molecular medicine 12, 99-101. Harvey, N.L., Daish, T., Mills, K., Dorstyn, L., Quinn, L.M., Read, S.H., Richardson, H., and Kumar, S. (2001). Characterization of the Drosophila caspase, DAMM. The Journal of biological chemistry 276, 25342-25350. Hawkins, C.J., Yoo, S.J., Peterson, E.P., Wang, S.L., Vernooy, S.Y., and Hay, B.A. (2000). The Drosophila caspase DRONC cleaves following glutamate or aspartate and is regulated by DIAP1, HID, and GRIM. The Journal of biological chemistry 275, 27084-27093. Hay, B.A., and Guo, M. (2006). Caspase-dependent cell death in Drosophila. Annual review of cell and developmental biology 22, 623-650. Hay, B.A., Wolff, T., and Rubin, G.M. (1994). Expression of baculovirus P35 prevents cell death in Drosophila. Development 120, 2121-2129. He, H., Jazdzewski, K., Li, W., Liyanarachchi, S., Nagy, R., Volinia, S., Calin, G.A., Liu, C.G., Franssila, K., Suster, S., et al. (2005a). The role of microRNA genes in papillary thyroid carcinoma. Proceedings of the National Academy of Sciences of the United States of America 102, 19075-19080. He, L., He, X., Lim, L.P., de Stanchina, E., Xuan, Z., Liang, Y., Xue, W., Zender, L., Magnus, J., Ridzon, D., et al. (2007). A microRNA component of the p53 tumour suppressor network. Nature 447, 1130-1134. He, L., Thomson, J.M., Hemann, M.T., Hernando-Monge, E., Mu, D., Goodson, S., Powers, S., Cordon-Cardo, C., Lowe, S.W., Hannon, G.J., et al. (2005b). A microRNA polycistron as a potential human oncogene. Nature 435, 828-833. Herman, M.A., She, P., Peroni, O.D., Lynch, C.J., and Kahn, B.B. (2010). Adipose tissue branched chain amino acid (BCAA) metabolism modulates circulating BCAA levels. The Journal of biological chemistry 285, 11348-11356. Hipfner, D.R., Weigmann, K., and Cohen, S.M. (2002). The bantam gene regulates Drosophila growth. Genetics 161, 1527-1537. Huang, J., Wu, S., Barrera, J., Matthews, K., and Pan, D. (2005). The Hippo signaling pathway coordinately regulates cell proliferation and apoptosis by inactivating Yorkie, the Drosophila Homolog of YAP. Cell 122, 421-434. Hutvagner, G., and Zamore, P.D. (2002). A microRNA in a multiple-turnover RNAi enzyme complex. Science 297, 2056-2060. Hwang, H.W., and Mendell, J.T. (2006). MicroRNAs in cell proliferation, cell death, and tumorigenesis. British journal of cancer 94, 776-780. Jaklevic, B., Uyetake, L., Wichmann, A., Bilak, A., English, C.N., and Su, T.T. (2008). Modulation of ionizing radiation-induced apoptosis by bantam microRNA in Drosophila. Developmental biology 320, 122-130. Jaklevic, B.R., and Su, T.T. (2004). Relative contribution of DNA repair, cell cycle checkpoints, and cell death to survival after DNA damage in Drosophila larvae. Current biology : CB 14, 23-32. Jovanovic, M., and Hengartner, M.O. (2006). miRNAs and apoptosis: RNAs to die for. Oncogene 25, 6176-6187. Kango-Singh, M., and Singh, A. (2009). Regulation of organ size: insights from the Drosophila Hippo signaling pathway. Developmental dynamics : an official publication of the American Association of Anatomists 238, 1627-1637. Kiger, J.A., Jr., Natzle, J.E., and Green, M.M. (2001). Hemocytes are essential for wing maturation in Drosophila melanogaster. Proceedings of the National Academy of Sciences of the United States of America 98, 10190-10195. Kiger, J.A., Jr., Natzle, J.E., Kimbrell, D.A., Paddy, M.R., Kleinhesselink, K., and Green, M.M. (2007). Tissue remodeling during maturation of the Drosophila wing. Developmental biology 301, 178-191. Kurada, P., and White, K. (1998). Ras promotes cell survival in Drosophila by downregulating hid expression. Cell 95, 319-329. Lai, E.C., Tomancak, P., Williams, R.W., and Rubin, G.M. (2003). Computational identification of Drosophila microRNA genes. Genome biology 4, R42. Leaman, D., Chen, P.Y., Fak, J., Yalcin, A., Pearce, M., Unnerstall, U., Marks, D.S., Sander, C., Tuschl, T., and Gaul, U. (2005). Antisense-mediated depletion reveals essential and specific functions of microRNAs in Drosophila development. Cell 121, 1097-1108. Lee, Y., Ahn, C., Han, J., Choi, H., Kim, J., Yim, J., Lee, J., Provost, P., Radmark, O., Kim, S., et al. (2003). The nuclear RNase III Drosha initiates microRNA processing. Nature 425, 415-419. Lee, Y., Kim, M., Han, J., Yeom, K.H., Lee, S., Baek, S.H., and Kim, V.N. (2004). MicroRNA genes are transcribed by RNA polymerase II. The EMBO journal 23, 4051-4060. Leulier, F., Ribeiro, P.S., Palmer, E., Tenev, T., Takahashi, K., Robertson, D., Zachariou, A., Pichaud, F., Ueda, R., and Meier, P. (2006). Systematic in vivo RNAi analysis of putative components of the Drosophila cell death machinery. Cell death and differentiation 13, 1663-1674. Liu, J., Li, C., Yu, Z., Huang, P., Wu, H., Wei, C., Zhu, N., Shen, Y., Chen, Y., Zhang, B., et al. (2012). Efficient and specific modifications of the Drosophila genome by means of an easy TALEN strategy. Journal of genetics and genomics = Yi chuan xue bao 39, 209-215. Lum, J.J., Bauer, D.E., Kong, M., Harris, M.H., Li, C., Lindsten, T., and Thompson, C.B. (2005). Growth factor regulation of autophagy and cell survival in the absence of apoptosis. Cell 120, 237-248. Macias, A., Romero, N.M., Martin, F., Suarez, L., Rosa, A.L., and Morata, G. (2004). PVF1/PVR signaling and apoptosis promotes the rotation and dorsal closure of the Drosophila male terminalia. The International journal of developmental biology 48, 1087-1094. Martinez, J., Patkaniowska, A., Urlaub, H., Luhrmann, R., and Tuschl, T. (2002). Single-stranded antisense siRNAs guide target RNA cleavage in RNAi. Cell 110, 563-574. McNeill, H., and Downward, J. (1999). Apoptosis: Ras to the rescue in the fly eye. Current biology : CB 9, R176-179. Meier, P., Silke, J., Leevers, S.J., and Evan, G.I. (2000). The Drosophila caspase DRONC is regulated by DIAP1. The EMBO journal 19, 598-611. Mendell, J.T. (2005). MicroRNAs: critical regulators of development, cellular physiology and malignancy. Cell cycle 4, 1179-1184. Nairz, K., Rottig, C., Rintelen, F., Zdobnov, E., Moser, M., and Hafen, E. (2006). Overgrowth caused by misexpression of a microRNA with dispensable wild-type function. Developmental biology 291, 314-324. Nicklin, P., Bergman, P., Zhang, B., Triantafellow, E., Wang, H., Nyfeler, B., Yang, H., Hild, M., Kung, C., Wilson, C., et al. (2009). Bidirectional transport of amino acids regulates mTOR and autophagy. Cell 136, 521-534. Nolo, R., Morrison, C.M., Tao, C., Zhang, X., and Halder, G. (2006). The bantam microRNA is a target of the hippo tumor-suppressor pathway. Current biology : CB 16, 1895-1904. Oh, H., and Irvine, K.D. (2009). In vivo analysis of Yorkie phosphorylation sites. Oncogene 28, 1916-1927. Ollmann, M., Young, L.M., Di Como, C.J., Karim, F., Belvin, M., Robertson, S., Whittaker, K., Demsky, M., Fisher, W.W., Buchman, A., et al. (2000). Drosophila p53 is a structural and functional homolog of the tumor suppressor p53. Cell 101, 91-101. Olsen, P.H., and Ambros, V. (1999). The lin-4 regulatory RNA controls developmental timing in Caenorhabditis elegans by blocking LIN-14 protein synthesis after the initiation of translation. Developmental biology 216, 671-680. Peterson, C., Carney, G.E., Taylor, B.J., and White, K. (2002). reaper is required for neuroblast apoptosis during Drosophila development. Development 129, 1467-1476. Piper, M.D., Selman, C., McElwee, J.J., and Partridge, L. (2008). Separating cause from effect: how does insulin/IGF signalling control lifespan in worms, flies and mice? Journal of internal medicine 263, 179-191. Rodriguez, A., Oliver, H., Zou, H., Chen, P., Wang, X., and Abrams, J.M. (1999). Dark is a Drosophila homologue of Apaf-1/CED-4 and functions in an evolutionarily conserved death pathway. Nature cell biology 1, 272-279. Ruvkun, G. (2001). Molecular biology. Glimpses of a tiny RNA world. Science 294, 797-799. Schoenherr, J.A., Drennan, J.M., Martinez, J.S., Chikka, M.R., Hall, M.C., Chang, H.C., and Clemens, J.C. (2012). Drosophila activated Cdc42 kinase has an anti-apoptotic function. PLoS genetics 8, e1002725. Shlevkov, E., and Morata, G. (2012). A dp53/JNK-dependant feedback amplification loop is essential for the apoptotic response to stress in Drosophila. Cell death and differentiation 19, 451-460. Slack, F.J., and Weidhaas, J.B. (2006). MicroRNAs as a potential magic bullet in cancer. Future oncology 2, 73-82. Song, Z., Guan, B., Bergman, A., Nicholson, D.W., Thornberry, N.A., Peterson, E.P., and Steller, H. (2000). Biochemical and genetic interactions between Drosophila caspases and the proapoptotic genes rpr, hid, and grim. Molecular and cellular biology 20, 2907-2914. Song, Z., McCall, K., and Steller, H. (1997). DCP-1, a Drosophila cell death protease essential for development. Science 275, 536-540. Stark, A., Brennecke, J., Russell, R.B., and Cohen, S.M. (2003). Identification of Drosophila MicroRNA targets. PLoS biology 1, E60. Tan, H., Poidevin, M., Li, H., Chen, D., and Jin, P. (2012). MicroRNA-277 modulates the neurodegeneration caused by Fragile X premutation rCGG repeats. PLoS genetics 8, e1002681. Tang, G. (2005). siRNA and miRNA: an insight into RISCs. Trends in biochemical sciences 30, 106-114. Tenev, T., Zachariou, A., Wilson, R., Paul, A., and Meier, P. (2002). Jafrac2 is an IAP antagonist that promotes cell death by liberating Dronc from DIAP1. The EMBO journal 21, 5118-5129. Thompson, B.J., and Cohen, S.M. (2006). The Hippo pathway regulates the bantam microRNA to control cell proliferation and apoptosis in Drosophila. Cell 126, 767-774. Thompson, C.B. (1995). Apoptosis in the pathogenesis and treatment of disease. Science 267, 1456-1462. Valerio, A., D'Antona, G., and Nisoli, E. (2011). Branched-chain amino acids, mitochondrial biogenesis, and healthspan: an evolutionary perspective. Aging 3, 464-478. Verghese, S., Bedi, S., and Kango-Singh, M. (2012). Hippo signalling controls Dronc activity to regulate organ size in Drosophila. Cell death and differentiation 19, 1664-1676. Wakshlag, J.J., Kallfelz, F.A., Wakshlag, R.R., and Davenport, G.M. (2006). The effects of branched-chain amino acids on canine neoplastic cell proliferation and death. The Journal of nutrition 136, 2007S-2010S. Waldhuber, M., Emoto, K., and Petritsch, C. (2005). The Drosophila caspase DRONC is required for metamorphosis and cell death in response to irradiation and developmental signals. Mechanisms of development 122, 914-927. White, K., Grether, M.E., Abrams, J.M., Young, L., Farrell, K., and Steller, H. (1994). Genetic control of programmed cell death in Drosophila. Science 264, 677-683. White, K., Tahaoglu, E., and Steller, H. (1996). Cell killing by the Drosophila gene reaper. Science 271, 805-807. Wing, J.P., Schwartz, L.M., and Nambu, J.R. (2001). The RHG motifs of Drosophila Reaper and Grim are important for their distinct cell death-inducing abilities. Mechanisms of development 102, 193-203. Wolff, T., and Ready, D.F. (1991). Cell death in normal and rough eye mutants of Drosophila. Development 113, 825-839. Xu, P., Vernooy, S.Y., Guo, M., and Hay, B.A. (2003). The Drosophila microRNA Mir-14 suppresses cell death and is required for normal fat metabolism. Current biology : CB 13, 790-795. Yan, X., Sun, Q., Ji, J., Zhu, Y., Liu, Z., and Zhong, Q. (2012). Reconstitution of leucine-mediated autophagy via the mTORC1-Barkor pathway in vitro. Autophagy 8, 213-221. Yi, R., Qin, Y., Macara, I.G., and Cullen, B.R. (2003). Exportin-5 mediates the nuclear export of pre-microRNAs and short hairpin RNAs. Genes & development 17, 3011-3016. Yu, Z., Raabe, T., and Hecht, N.B. (2005). MicroRNA Mirn122a reduces expression of the posttranscriptionally regulated germ cell transition protein 2 (Tnp2) messenger RNA (mRNA) by mRNA cleavage. Biology of reproduction 73, 427-433. Zeng, Y., Wagner, E.J., and Cullen, B.R. (2002). Both natural and designed micro RNAs can inhibit the expression of cognate mRNAs when expressed in human cells. Molecular cell 9, 1327-1333. Zhang, H., Cai, X., Wang, Y., Tang, H., Tong, D., and Ji, F. (2010). microRNA-143, down-regulated in osteosarcoma, promotes apoptosis and suppresses tumorigenicity by targeting Bcl-2. Oncology reports 24, 1363-1369. Zhang, W., Qian, J.X., Yi, H.L., Yang, Z.D., Wang, C.F., Chen, J.Y., Wei, X.Z., Fu, Q., and Ma, H. (2012). The microRNA-29 plays a central role in osteosarcoma pathogenesis and progression. Molekuliarnaia biologiia 46, 622-627. Zhao, G., Cai, C., Yang, T., Qiu, X., Liao, B., Li, W., Ji, Z., Zhao, J., Zhao, H., Guo, M., et al. (2013). MicroRNA-221 induces cell survival and cisplatin resistance through PI3K/Akt pathway in human osteosarcoma. PloS one 8, e53906. Zhou, L., Schnitzler, A., Agapite, J., Schwartz, L.M., Steller, H., and Nambu, J.R. (1997). Cooperative functions of the reaper and head involution defective genes in the programmed cell death of Drosophila central nervous system midline cells. Proceedings of the National Academy of Sciences of the United States of America 94, 5131-5136. Zoncu, R., Efeyan, A., and Sabatini, D.M. (2011). mTOR: from growth signal integration to cancer, diabetes and ageing. Nature reviews Molecular cell biology 12, 21-35. | |
| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/55588 | - |
| dc.description.abstract | 在動物發育過程中，細胞死亡、生長和存活是彼此互相協調的。許多控制細胞生長和死亡的基因已經被確認，然而這些效應是如何連接在一起仍是未知的。在本篇研究中，藉由基因篩選，我們發現一個微型核醣核酸，miR-277，能夠抑制 hid誘導的細胞凋亡。異位表現miR-277能抑制在眼睛發育過程並且延緩在果蠅翅膀發展中產生的細胞死亡。我們預測了四個促進細胞凋亡基因為miR-277之標靶，包含 hid， dronc， dark和drice。 經由螢光素酶檢測和生物活體分析，我們證明過量表現miR-277能藉由靶擊 hid 和 dronc 進而專一性地抑制細胞凋亡。為了進一步確認這項發現，我們以TALEN的技術產生miR-277突變的果蠅品系。在異結合型或是同結合型miR-277突變的基因背景下，hid誘導的果蠅眼睛因凋亡而產生消融現象有被增強，進一步證實hid是miR-277的標靶基因。在電離輻射誘導的DNA損傷中，hid的mRNA增幅量在同結合型miR-277突變果蠅的三齡幼蟲中時程上有被延長的現象。hid下游的caspase 3的訊號因此增加，這意味著在照射電離輻射後，同結合型miR-277突變會促進細胞死亡。對於調節miR-277表現的上游訊號，我們證明過量表現yki 或是p53 並不會影響miR-277的表現，意味著miR-277很可能不是Hippo訊號路徑和p53的直接下游基因。前人研究證明miR-277在調控支鏈胺基酸 (branched chain amino acid, BCAA) 代謝路徑的開關中扮演重要角色。從生物資訊的搜索發現，在果蠅中幾乎所有參與支鏈胺基酸代謝的酵素都是miR-277可能的標靶基因。在本篇研究中，我們顯示在飢餓的情況下，與控制組相比，同結合型 miR-277 突變的果蠅增加平均存活率，這意味著miR-277 可能透過控制BCAA代謝路徑來參與生存的調節。在本篇研究中，我們也顯示以miRNA或是RNA干擾的方式下調在BCAA代謝中最主要的三個酵素或是CG5599 (其中一個主要的酵素) 能部份抑制 hid 但是不能抑制 rpr 和 grim 誘導的果蠅眼睛消融現象，這意味著 BCAA代謝路徑可能參與hid誘導的死亡。綜合上述，miR-277藉由調控hid、dronc和BCAA代謝路徑中的酵素進而在細胞死亡和存活中扮演重要的角色。這暗示著在對能量平衡的反應中，miR-277可能是連接細胞死亡與存活的橋樑。 | zh_TW |
| dc.description.abstract | Cell death, cell growth and survival are coordinated processes during development in animals. Although many genes that control cell growth and apoptosis have been identified, how these effectors are link the two cellular processes together remains unknown. In this study, we examined the roles of the microRNA, miR-277, in hid-induced cell death and in BCAA catabolism. Using a genetic screen, miR-277 was found to be able to regulate hid-induced cell death in D. melanogaster. Ectopic expression of miR-277 inhibits cell death during eye development and delays apoptosis during wing maturation. Overexpression of miR-277 in S2 cells and Drosophila eyes were found to inhibit apoptosis by targeting the putative apoptotic genes, hid and dronc, while TALEN-generated heterozygous and homozygous miR-277 mutants enhances hid-induced eye ablation as identified through a luciferase activity assay. Cell death is exacerbated when miR-277 homozygous mutant is exposed to ionization radiation (IR), as marked by prolonged hid transcript levels in third instar larvae and caspase 3 signals in wing imaginal discs. qPCR results indicate that yorkie and p53 are not upstream of miR-277 when the dominant active form of yorkie and p53 was overexpressed, suggesting miR-277 may not be involved in the Hippo or p53 pathway. In addition to the regulatory role of apoptosis, miR-277 has been identified that function importantly in activating branched chain amino acid (BCAA) catabolism. Bioinformatics analysis revealed that almost all enzymes within the BCAA catabolic pathway are predicted targets of miR-277 in Drosophila. In this study, we show that miR-277 homozygous mutant flies increase mean survival rate in both male and female compared to wild type under starvation, suggesting that miR-277 may participate importantly in the regulation of survival through controlling BCAA catabolism. Additionally, the knockdown of three major enzymes or CG5599 within BCAA catabolism using RNA interference partially inhibited hid but not rpr and grim-induced eye ablation, suggesting BCAA catabolism may involve in hid-induced death. In summary, miR-277 functions as an essential role in cell death and survival through regulating hid, dronc and enzymes within BCAA catabolism. Our results imply that miR-277 may function to link cell death and survival in response to energy homeostasis. | en |
| dc.description.provenance | Made available in DSpace on 2021-06-16T04:11:06Z (GMT). No. of bitstreams: 1 ntu-103-R01b43010-1.pdf: 5205607 bytes, checksum: c8097b79e59ed08f2a39deac2bb708e6 (MD5) Previous issue date: 2014 | en |
| dc.description.tableofcontents | TABLE of CONTENTS
致謝 I 中文摘要 II ABSTRACT IV TABLE of CONTENTS VI TABLE of FIGURES IX TABLE of TABLES XI INTRODUCTION 1 1. microRNAs 1 1.1 The relationship between microRNAs and programmed cell death 2 2. Drosophila programmed cell death 4 3. Drosophila microRNA-277 6 4. Branched chain amino acid (BCAA) metabolic pathway 7 4.1 The relationship between branched chain amino acid (BCAA) metabolic pathway and programmed cell death 8 5. The specific aims of this thesis 9 MATERIALS and METHODS 10 1. Flies stocks 10 1.1. Generation of transgenic flies 10 1.2. miR-277 TALEN mutants 10 2. Immunostaining 11 3. Quantitative real-time PCR (qRT-PCR) analysis 12 4. Northern blot analysis 13 5. Scanning Electron Microscopy (SEM) 14 6. Starvation Test 14 RESULTS 15 DISCUSSIONS and CONCLUSIONS 33 REFERENCES 43 FIGURES 58 TABLES 83 APPENDIXES 91 Appendix 1. The crossing scheme of miR-277 mutant strains generated by TALEN. 91 Appendix 2. Overexpression of miR-277 Caused Cell Death Defect during Eye and Wing Development. 93 Appendix 3. hid, dronc and dark are the Putative Target Genes of miR-277. 95 Appendix 4. Hippo Signaling Pathway is the Upstream of Main Apoptosis Pathway, whereas miR-277 Overexpression did not Rescued hippo-Induced Apoptosis. 97 Appendix 5. p53 Overexpression Induces Apoptosis through the Main Apoptosis Pathway in Drosophila. 99 Appendix 6. p53 may not be the Downstream of Apoptosis Pathway or JNK pathway. 101 Appendix 7. P53 was not Up-regulated in hep, hid, reaper (rpr) and dronc Overexpression Eye Imaginal Discs. 102 | |
| dc.language.iso | en | |
| dc.subject | 支鏈胺基酸代謝 | zh_TW |
| dc.subject | 黑腹果蠅 | zh_TW |
| dc.subject | X光照射 | zh_TW |
| dc.subject | 微型核醣核酸miR-277 | zh_TW |
| dc.subject | 細胞凋亡 | zh_TW |
| dc.subject | X-ray | en |
| dc.subject | Drosophila melanogaster | en |
| dc.subject | miR-277 | en |
| dc.subject | apoptosis | en |
| dc.subject | BCAA catabolism | en |
| dc.title | 探討微型核醣核酸 miR-277 在果蠅細胞凋亡所扮演的角色 | zh_TW |
| dc.title | The Roles of miR-277 During Apoptosis in Drosophila | en |
| dc.type | Thesis | |
| dc.date.schoolyear | 102-2 | |
| dc.description.degree | 碩士 | |
| dc.contributor.oralexamcommittee | 吳益群(Yi-Chun Wu),詹世鵬(Shih-Peng Chan),陳光超(Guang-Chao Chen),蔡玉真(Yu-Chen Tsai) | |
| dc.subject.keyword | 黑腹果蠅,微型核醣核酸miR-277,細胞凋亡,支鏈胺基酸代謝,X光照射, | zh_TW |
| dc.subject.keyword | Drosophila melanogaster,miR-277,apoptosis,BCAA catabolism,X-ray, | en |
| dc.relation.page | 102 | |
| dc.rights.note | 有償授權 | |
| dc.date.accepted | 2014-08-21 | |
| 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 | |
文件中的檔案：
| 檔案 | 大小 | 格式 | |
|---|---|---|---|
| ntu-103-1.pdf 未授權公開取用 | 5.08 MB | Adobe PDF |
系統中的文件，除了特別指名其著作權條款之外，均受到著作權保護，並且保留所有的權利。