MicroRNA (miRNA)是內源性非編碼的單股小RNA，藉由與mRNA結合來抑制其mRNA的轉譯或使其降解而負調控基因的表現。近年研究顯示miRNA在多種腫瘤與正常組織間表現量不同且與癌症形成有關。miRNA藉由改變與腫瘤形成相關基因的表現量而作為腫瘤抑制基因或是致癌基因。實驗室先前藉由微陣列方式發現miR-320在口腔癌細胞株(OC2)的表現量比在正常人類口腔角質細胞中表現量低。在分析臨床口腔癌病人的腫瘤組織與非腫瘤組織的配對檢體中也發現，mir-320在腫瘤組織中的表現量比在非腫瘤組織中明顯減少。藉由軟體分析，結果預測neuropilin 1 (NRP1)可能為miR-320調控的標的基因。NRP1在神經及血管發展扮演重要角色，它可作為一受體與軸突導向分子semaphorine家族或血管新生刺激因子VEGF家族結合。在許多文獻指出NRP1會促進腫瘤血管新生、血管內皮細胞的移行以及腫瘤轉移。在此研究我們進一步分析miR-320是否會調控NRP1在後轉錄階段的表現，結果發現將miR-320的前驅分子或抑制劑送入人類臍帶血管內皮細胞(HUVECs) 中皆能影響NRP1的表現，利用報導基因表現分析也證實miR-320確實可透過結合在NRP1的3’UTR上而影響冷光表現。我們發現miR-320可藉由減少NRP1表現而抑制血管內皮細胞的移行及貼附。此外，我們發現血管內皮細胞在缺氧以及養分缺乏下miR-320表現量會下降且NRP1表現量會上升。利用in situ hybridization及免疫組織化學染色分析臨床檢體發現在OSCC組織中的血管其miR-320表現下降並與NRP1表現具有相關性。綜合以上結果顯示，miR-320在腫瘤組織中的血管內皮細胞表現量減少可能參與調節腫瘤血管新生的功能。

MicroRNAs (miRNAs) are endogenous small noncoding RNAs that reduce the translation of mRNAs or cause mRNA degradation by targeting mRNAs. Recent evidences have shown that a number of miRNAs are differentially expressed in various tumors vs. normal tissues and associated with cancer development. MiRNAs change in the amounts of these RNAs can be tumorigenic or tumor suppressive if they target mRNAs for either a tumor suppressor or an oncogene. In the previous study, we found that the expression of miR-320 was lower in oral cancer cells (OC2) than in normal human oral keratinocytes by microarray analyses. In the analysis of clinical OSCC match-pair tissues, we also found that miR-320 were significantly down-regulated in oral cancer specimens. By using the bioinformatic tools at the miRNA target database, neuropilin 1 (NRP1) was predicted to be a target of miR-320. NRP1 plays a central role in neuronal and blood vessel development as a receptor for two ligand types, the semaphorin family of axon guidance modulators and the VEGF family of angiogenesis stimulators. Several studies showed that NRP1 promoted tumor angiogenesis, vascular endothelial cells migration, and tumor metastasis. In this study, we found that miR-320 regulates the expression of NRP1 at a posttranscriptional level by transfecting miR-320 precursor or antagomiR-320 in human umbilical vein endothelial cells (HUVECs). Using luciferase reporter assays we confirmed that miR-320 could reduce luciferase expression by binding 3’ UTR of NRP1. MiR-320 reduced HUVECs migration and adhesion by decreasing expression of NRP1. Furthermore, we found that hypoxia-nutrients deprivation reduced expression of miR-320 and increase NRP1 level in HUVECs. Clinical specimens’ examination by in situ hybridization and immunohistochemistry analyses also showed that miR-320 expression was down-regulated and inversely correlated with NRP1 expression status in the blood vessels of OSCC tissues. Taken together, our present study revealed that miR-320 was down-regulated in cancer-associated vascular endothelial cells and might modulate tumor angiogenesis.

Arany, Z., Huang, L.E., Eckner, R., Bhattacharya, S., Jiang, C., Goldberg, M.A., Bunn, H.F., and Livingston, D.M. (1996). An essential role for p300/CBP in the cellular response to hypoxia. Proc Natl Acad Sci U S A 93, 12969-12973.
Bachelder, R.E., Crago, A., Chung, J., Wendt, M.A., Shaw, L.M., Robinson, G., and Mercurio, A.M. (2001). Vascular endothelial growth factor is an autocrine survival factor for neuropilin-expressing breast carcinoma cells. Cancer Res 61, 5736-5740.
Bachelder, R.E., Lipscomb, E.A., Lin, X., Wendt, M.A., Chadborn, N.H., Eickholt, B.J., and Mercurio, A.M. (2003). Competing autocrine pathways involving alternative neuropilin-1 ligands regulate chemotaxis of carcinoma cells. Cancer Res 63, 5230-5233.
Bartel, D.P. (2004). MicroRNAs: genomics, biogenesis, mechanism, and function. Cell 116, 281-297.
Baskerville, S., and Bartel, D.P. (2005). Microarray profiling of microRNAs reveals frequent coexpression with neighboring miRNAs and host genes. RNA 11, 241-247.
Bernstein, E., Caudy, A.A., Hammond, S.M., and Hannon, G.J. (2001). Role for a bidentate ribonuclease in the initiation step of RNA interference. Nature 409, 363-366.
Calin, G.A., Dumitru, C.D., Shimizu, M., Bichi, R., Zupo, S., Noch, E., Aldler, H., Rattan, S., Keating, M., Rai, K., et al. (2002). Frequent deletions and down-regulation of micro- RNA genes miR15 and miR16 at 13q14 in chronic lymphocytic leukemia. Proc Natl Acad Sci U S A 99, 15524-15529.
Carmeliet, P. (2000). Mechanisms of angiogenesis and arteriogenesis. Nat Med 6, 389-395.
Chen, C.Y., Gherzi, R., Ong, S.E., Chan, E.L., Raijmakers, R., Pruijn, G.J., Stoecklin, G., Moroni, C., Mann, M., and Karin, M. (2001). AU binding proteins recruit the exosome to degrade ARE-containing mRNAs. Cell 107, 451-464.
Chen, C.Y., and Shyu, A.B. (1995). AU-rich elements: characterization and importance in mRNA degradation. Trends Biochem Sci 20, 465-470.
Chen, C.Z., Li, L., Lodish, H.F., and Bartel, D.P. (2004). MicroRNAs modulate hematopoietic lineage differentiation. Science 303, 83-86.
Chen, Y., and Gorski, D.H. (2008). Regulation of angiogenesis through a microRNA (miR-130a) that down-regulates antiangiogenic homeobox genes GAX and HOXA5. Blood 111, 1217-1226.
Cheng, A.M., Byrom, M.W., Shelton, J., and Ford, L.P. (2005). Antisense inhibition of human miRNAs and indications for an involvement of miRNA in cell growth and apoptosis. Nucleic Acids Res 33, 1290-1297.
Choi, K.S., Bae, M.K., Jeong, J.W., Moon, H.E., and Kim, K.W. (2003). Hypoxia-induced angiogenesis during carcinogenesis. J Biochem Mol Biol 36, 120-127.
Eliceiri, B.P., and Cheresh, D.A. (2001). Adhesion events in angiogenesis. Curr Opin Cell Biol 13, 563-568.
Ellis, L.M. (2006). The role of neuropilins in cancer. Mol Cancer Ther 5, 1099-1107.
Endres, M., Meisel, A., Biniszkiewicz, D., Namura, S., Prass, K., Ruscher, K., Lipski, A., Jaenisch, R., Moskowitz, M.A., and Dirnagl, U. (2000). DNA methyltransferase contributes to delayed ischemic brain injury. J Neurosci 20, 3175-3181.
Fasanaro, P., D'Alessandra, Y., Di Stefano, V., Melchionna, R., Romani, S., Pompilio, G., Capogrossi, M.C., and Martelli, F. (2008). MicroRNA-210 modulates endothelial cell response to hypoxia and inhibits the receptor tyrosine kinase ligand Ephrin-A3. J Biol Chem 283, 15878-15883.
Folkman, J. (1995). Angiogenesis in cancer, vascular, rheumatoid and other disease. Nat Med 1, 27-31.
Forsythe, J.A., Jiang, B.H., Iyer, N.V., Agani, F., Leung, S.W., Koos, R.D., and Semenza, G.L. (1996). Activation of vascular endothelial growth factor gene transcription by hypoxia-inducible factor 1. Mol Cell Biol 16, 4604-4613.
Fujisawa, H., Kitsukawa, T., Kawakami, A., Takagi, S., Shimizu, M., and Hirata, T. (1997). Roles of a neuronal cell-surface molecule, neuropilin, in nerve fiber fasciculation and guidance. Cell Tissue Res 290, 465-470.
Geretti, E., Shimizu, A., and Klagsbrun, M. (2008). Neuropilin structure governs VEGF and semaphorin binding and regulates angiogenesis. Angiogenesis 11, 31-39.
Griffioen, A.W., and Molema, G. (2000). Angiogenesis: potentials for pharmacologic intervention in the treatment of cancer, cardiovascular diseases, and chronic inflammation. Pharmacol Rev 52, 237-268.
Griffiths-Jones, S. (2004). The microRNA Registry. Nucleic Acids Res 32, D109-111.
Gu, C., Limberg, B.J., Whitaker, G.B., Perman, B., Leahy, D.J., Rosenbaum, J.S., Ginty, D.D., and Kolodkin, A.L. (2002). Characterization of neuropilin-1 structural features that confer binding to semaphorin 3A and vascular endothelial growth factor 165. J Biol Chem 277, 18069-18076.
Hammond, S.M., Boettcher, S., Caudy, A.A., Kobayashi, R., and Hannon, G.J. (2001). Argonaute2, a link between genetic and biochemical analyses of RNAi. Science 293, 1146-1150.
Hanahan, D., and Folkman, J. (1996). Patterns and emerging mechanisms of the angiogenic switch during tumorigenesis. Cell 86, 353-364.
He, L., and Hannon, G.J. (2004). MicroRNAs: small RNAs with a big role in gene regulation. Nat Rev Genet 5, 522-531.
He, Z., and Tessier-Lavigne, M. (1997). Neuropilin is a receptor for the axonal chemorepellent Semaphorin III. Cell 90, 739-751.
Hong, T.M., Chen, Y.L., Wu, Y.Y., Yuan, A., Chao, Y.C., Chung, Y.C., Wu, M.H., Yang, S.C., Pan, S.H., Shih, J.Y., et al. (2007). Targeting neuropilin 1 as an antitumor strategy in lung cancer. Clin Cancer Res 13, 4759-4768.
Hu, B., Guo, P., Bar-Joseph, I., Imanishi, Y., Jarzynka, M.J., Bogler, O., Mikkelsen, T., Hirose, T., Nishikawa, R., and Cheng, S.Y. (2007). Neuropilin-1 promotes human glioma progression through potentiating the activity of the HGF/SF autocrine pathway. Oncogene 26, 5577-5586.
Hu, C.J., Chen, S.D., Yang, D.I., Lin, T.N., Chen, C.M., Huang, T.H., and Hsu, C.Y. (2006). Promoter region methylation and reduced expression of thrombospondin-1 after oxygen-glucose deprivation in murine cerebral endothelial cells. J Cereb Blood Flow Metab 26, 1519-1526.
Hynes, R.O. (2007). Cell-matrix adhesion in vascular development. J Thromb Haemost 5 Suppl 1, 32-40.
Ishihama, H., Ohbayashi, M., Kurosawa, N., Kitsukawa, T., Matsuura, O., Miyake, Y., and Muramatsu, T. (2001). Colocalization of neuropilin-1 and Flk-1 in retinal neovascularization in a mouse model of retinopathy. Invest Ophthalmol Vis Sci 42, 1172-1178.
Jing, Q., Huang, S., Guth, S., Zarubin, T., Motoyama, A., Chen, J., Di Padova, F., Lin, S.C., Gram, H., and Han, J. (2005). Involvement of microRNA in AU-rich element-mediated mRNA instability. Cell 120, 623-634.
Karp, X., and Ambros, V. (2005). Developmental biology. Encountering microRNAs in cell fate signaling. Science 310, 1288-1289.
Kawakami, A., Kitsukawa, T., Takagi, S., and Fujisawa, H. (1996). Developmentally regulated expression of a cell surface protein, neuropilin, in the mouse nervous system. J Neurobiol 29, 1-17.
Kawasaki, T., Kitsukawa, T., Bekku, Y., Matsuda, Y., Sanbo, M., Yagi, T., and Fujisawa, H. (1999). A requirement for neuropilin-1 in embryonic vessel formation. Development 126, 4895-4902.
Khvorova, A., Reynolds, A., and Jayasena, S.D. (2003). Functional siRNAs and miRNAs exhibit strand bias. Cell 115, 209-216.
Kitsukawa, T., Shimono, A., Kawakami, A., Kondoh, H., and Fujisawa, H. (1995). Overexpression of a membrane protein, neuropilin, in chimeric mice causes anomalies in the cardiovascular system, nervous system and limbs. Development 121, 4309-4318.
Kolodkin, A.L., Levengood, D.V., Rowe, E.G., Tai, Y.T., Giger, R.J., and Ginty, D.D. (1997). Neuropilin is a semaphorin III receptor. Cell 90, 753-762.
Kondo, K., and Kaelin, W.G., Jr. (2001). The von Hippel-Lindau tumor suppressor gene. Exp Cell Res 264, 117-125.
Kuehbacher, A., Urbich, C., Zeiher, A.M., and Dimmeler, S. (2007). Role of Dicer and Drosha for endothelial microRNA expression and angiogenesis. Circ Res 101, 59-68.
Lagos-Quintana, M., Rauhut, R., Lendeckel, W., and Tuschl, T. (2001). Identification of novel genes coding for small expressed RNAs. Science 294, 853-858.
Lando, D., Peet, D.J., Gorman, J.J., Whelan, D.A., Whitelaw, M.L., and Bruick, R.K. (2002). FIH-1 is an asparaginyl hydroxylase enzyme that regulates the transcriptional activity of hypoxia-inducible factor. Genes Dev 16, 1466-1471.
Lee, R.C., and Ambros, V. (2001). An extensive class of small RNAs in Caenorhabditis elegans. Science 294, 862-864.
Lee, R.C., Feinbaum, R.L., and Ambros, V. (1993). The C. elegans heterochronic gene lin-4 encodes small RNAs with antisense complementarity to lin-14. Cell 75, 843-854.
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. EMBO J 23, 4051-4060.
Lim, L.P., Glasner, M.E., Yekta, S., Burge, C.B., and Bartel, D.P. (2003). Vertebrate microRNA genes. Science 299, 1540.
Liu, Y., Cox, S.R., Morita, T., and Kourembanas, S. (1995). Hypoxia regulates vascular endothelial growth factor gene expression in endothelial cells. Identification of a 5' enhancer. Circ Res 77, 638-643.
Liu, C.J. (2008). The role of miR-320 and miR-185 in oral cancer progression. Masteral thesis. Institute of Oral Medicine, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
Lubarsky, B., and Krasnow, M.A. (2003). Tube morphogenesis: making and shaping biological tubes. Cell 112, 19-28.
Mahon, P.C., Hirota, K., and Semenza, G.L. (2001). FIH-1: a novel protein that interacts with HIF-1alpha and VHL to mediate repression of HIF-1 transcriptional activity. Genes Dev 15, 2675-2686.
Maziere, P., and Enright, A.J. (2007). Prediction of microRNA targets. Drug Discov Today 12, 452-458.
Miao, H.Q., and Klagsbrun, M. (2000). Neuropilin is a mediator of angiogenesis. Cancer Metastasis Rev 19, 29-37.
Miao, H.Q., Lee, P., Lin, H., Soker, S., and Klagsbrun, M. (2000). Neuropilin-1 expression by tumor cells promotes tumor angiogenesis and progression. FASEB J 14, 2532-2539.
Miao, H.Q., Soker, S., Feiner, L., Alonso, J.L., Raper, J.A., and Klagsbrun, M. (1999). Neuropilin-1 mediates collapsin-1/semaphorin III inhibition of endothelial cell motility: functional competition of collapsin-1 and vascular endothelial growth factor-165. J Cell Biol 146, 233-242.
Mizukami, Y., Li, J., Zhang, X., Zimmer, M.A., Iliopoulos, O., and Chung, D.C. (2004). Hypoxia-inducible factor-1-independent regulation of vascular endothelial growth factor by hypoxia in colon cancer. Cancer Res 64, 1765-1772.
Mukherjee, D., Gao, M., O'Connor, J.P., Raijmakers, R., Pruijn, G., Lutz, C.S., and Wilusz, J. (2002). The mammalian exosome mediates the efficient degradation of mRNAs that contain AU-rich elements. EMBO J 21, 165-174.
Murga, M., Fernandez-Capetillo, O., and Tosato, G. (2005). Neuropilin-1 regulates attachment in human endothelial cells independently of vascular endothelial growth factor receptor-2. Blood 105, 1992-1999.
Pan, Q., Chanthery, Y., Liang, W.C., Stawicki, S., Mak, J., Rathore, N., Tong, R.K., Kowalski, J., Yee, S.F., Pacheco, G., et al. (2007a). Blocking neuropilin-1 function has an additive effect with anti-VEGF to inhibit tumor growth. Cancer Cell 11, 53-67.
Pan, Q., Chathery, Y., Wu, Y., Rathore, N., Tong, R.K., Peale, F., Bagri, A., Tessier-Lavigne, M., Koch, A.W., and Watts, R.J. (2007b). Neuropilin-1 binds to VEGF121 and regulates endothelial cell migration and sprouting. J Biol Chem 282, 24049-24056.
Parikh, A.A., Fan, F., Liu, W.B., Ahmad, S.A., Stoeltzing, O., Reinmuth, N., Bielenberg, D., Bucana, C.D., Klagsbrun, M., and Ellis, L.M. (2004). Neuropilin-1 in human colon cancer: expression, regulation, and role in induction of angiogenesis. Am J Pathol 164, 2139-2151.
Pasquinelli, A.E., Reinhart, B.J., Slack, F., Martindale, M.Q., Kuroda, M.I., Maller, B., Hayward, D.C., Ball, E.E., Degnan, B., Muller, P., et al. (2000). Conservation of the sequence and temporal expression of let-7 heterochronic regulatory RNA. Nature 408, 86-89.
Poliseno, L., Tuccoli, A., Mariani, L., Evangelista, M., Citti, L., Woods, K., Mercatanti, A., Hammond, S., and Rainaldi, G. (2006). MicroRNAs modulate the angiogenic properties of HUVECs. Blood 108, 3068-3071.
Poy, M.N., Eliasson, L., Krutzfeldt, J., Kuwajima, S., Ma, X., Macdonald, P.E., Pfeffer, S., Tuschl, T., Rajewsky, N., Rorsman, P., et al. (2004). A pancreatic islet-specific microRNA regulates insulin secretion. Nature 432, 226-230.
Prokopczyk, B., Rivenson, A., Bertinato, P., Brunnemann, K.D., and Hoffmann, D. (1987). 3-(Methylnitrosamino)propionitrile: occurrence in saliva of betel quid chewers, carcinogenicity, and DNA methylation in F344 rats. Cancer Res 47, 467-471.
Ravi, R., Mookerjee, B., Bhujwalla, Z.M., Sutter, C.H., Artemov, D., Zeng, Q., Dillehay, L.E., Madan, A., Semenza, G.L., and Bedi, A. (2000). Regulation of tumor angiogenesis by p53-induced degradation of hypoxia-inducible factor 1alpha. Genes Dev 14, 34-44.
Ren, X.P., Wu, J., Wang, X., Sartor, M.A., Qian, J., Jones, K., Nicolaou, P., Pritchard, T.J., and Fan, G.C. (2009). MicroRNA-320 is involved in the regulation of cardiac ischemia/reperfusion injury by targeting heat-shock protein 20. Circulation 119, 2357-2366.
Risau, W., and Lemmon, V. (1988). Changes in the vascular extracellular matrix during embryonic vasculogenesis and angiogenesis. Dev Biol 125, 441-450.
Schmidt, D., Textor, B., Pein, O.T., Licht, A.H., Andrecht, S., Sator-Schmitt, M., Fusenig, N.E., Angel, P., and Schorpp-Kistner, M. (2007). Critical role for NF-kappaB-induced JunB in VEGF regulation and tumor angiogenesis. EMBO J 26, 710-719.
Semenza, G.L. (2004). Hydroxylation of HIF-1: oxygen sensing at the molecular level. Physiology (Bethesda) 19, 176-182.
Semenza, G.L. (2007). Vasculogenesis, angiogenesis, and arteriogenesis: mechanisms of blood vessel formation and remodeling. J Cell Biochem 102, 840-847.
Shimizu, M., Murakami, Y., Suto, F., and Fujisawa, H. (2000). Determination of cell adhesion sites of neuropilin-1. J Cell Biol 148, 1283-1293.
Soker, S., Miao, H.Q., Nomi, M., Takashima, S., and Klagsbrun, M. (2002). VEGF165 mediates formation of complexes containing VEGFR-2 and neuropilin-1 that enhance VEGF165-receptor binding. J Cell Biochem 85, 357-368.
Soker, S., Takashima, S., Miao, H.Q., Neufeld, G., and Klagsbrun, M. (1998). Neuropilin-1 is expressed by endothelial and tumor cells as an isoform-specific receptor for vascular endothelial growth factor. Cell 92, 735-745.
Stoeltzing, O., McCarty, M.F., Wey, J.S., Fan, F., Liu, W., Belcheva, A., Bucana, C.D., Semenza, G.L., and Ellis, L.M. (2004). Role of hypoxia-inducible factor 1alpha in gastric cancer cell growth, angiogenesis, and vessel maturation. J Natl Cancer Inst 96, 946-956.
Suarez, Y., Fernandez-Hernando, C., Pober, J.S., and Sessa, W.C. (2007). Dicer dependent microRNAs regulate gene expression and functions in human endothelial cells. Circ Res 100, 1164-1173.
Takagi, S., Hirata, T., Agata, K., Mochii, M., Eguchi, G., and Fujisawa, H. (1991). The A5 antigen, a candidate for the neuronal recognition molecule, has homologies to complement components and coagulation factors. Neuron 7, 295-307.
Takagi, S., Kasuya, Y., Shimizu, M., Matsuura, T., Tsuboi, M., Kawakami, A., and Fujisawa, H. (1995). Expression of a cell adhesion molecule, neuropilin, in the developing chick nervous system. Dev Biol 170, 207-222.
Takagi, S., Tsuji, T., Amagai, T., Takamatsu, T., and Fujisawa, H. (1987). Specific cell surface labels in the visual centers of Xenopus laevis tadpole identified using monoclonal antibodies. Dev Biol 122, 90-100.
Tang, N., Wang, L., Esko, J., Giordano, F.J., Huang, Y., Gerber, H.P., Ferrara, N., and Johnson, R.S. (2004). Loss of HIF-1alpha in endothelial cells disrupts a hypoxia-driven VEGF autocrine loop necessary for tumorigenesis. Cancer Cell 6, 485-495.
Urbich, C., Kuehbacher, A., and Dimmeler, S. (2008). Role of microRNAs in vascular diseases, inflammation, and angiogenesis. Cardiovasc Res 79, 581-588.
Valdembri, D., Caswell, P.T., Anderson, K.I., Schwarz, J.P., Konig, I., Astanina, E., Caccavari, F., Norman, J.C., Humphries, M.J., Bussolino, F., et al. (2009). Neuropilin-1/GIPC1 signaling regulates alpha5beta1 integrin traffic and function in endothelial cells. PLoS Biol 7, e25.
Wang, L., Zeng, H., Wang, P., Soker, S., and Mukhopadhyay, D. (2003). Neuropilin-1-mediated vascular permeability factor/vascular endothelial growth factor-dependent endothelial cell migration. J Biol Chem 278, 48848-48860.
Wang, X.H., Qian, R.Z., Zhang, W., Chen, S.F., Jin, H.M., and Hu, R.M. (2009). MicroRNA-320 expression in myocardial microvascular endothelial cells and its relationship with insulin-like growth factor-1 in type 2 diabetic rats. Clin Exp Pharmacol Physiol 36, 181-188.
Wey, J.S., Gray, M.J., Fan, F., Belcheva, A., McCarty, M.F., Stoeltzing, O., Somcio, R., Liu, W., Evans, D.B., Klagsbrun, M., et al. (2005). Overexpression of neuropilin-1 promotes constitutive MAPK signalling and chemoresistance in pancreatic cancer cells. Br J Cancer 93, 233-241.
Wightman, B., Ha, I., and Ruvkun, G. (1993). Posttranscriptional regulation of the heterochronic gene lin-14 by lin-4 mediates temporal pattern formation in C. elegans. Cell 75, 855-862.
Wu, L., Fan, J., and Belasco, J.G. (2006). MicroRNAs direct rapid deadenylation of mRNA. Proc Natl Acad Sci U S A 103, 4034-4039.
Xu, P., Guo, M., and Hay, B.A. (2004). MicroRNAs and the regulation of cell death. Trends Genet 20, 617-624.
Yamagishi, H., Olson, E.N., and Srivastava, D. (2000). The basic helix-loop-helix transcription factor, dHAND, is required for vascular development. J Clin Invest 105, 261-270.
Yang, M.H., Wu, M.Z., Chiou, S.H., Chen, P.M., Chang, S.Y., Liu, C.J., Teng, S.C., and Wu, K.J. (2008). Direct regulation of TWIST by HIF-1alpha promotes metastasis. Nat Cell Biol 10, 295-305.
Ying, S.Y., and Lin, S.L. (2005). Intronic microRNAs. Biochem Biophys Res Commun 326, 515-520.
Ying, N.W. (2008). The role of galectin-1 on human vascular endothelium permeability. Masteral thesis. Institute of Oral Medicine, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
Zeng, Y., and Cullen, B.R. (2004). Structural requirements for pre-microRNA binding and nuclear export by Exportin 5. Nucleic Acids Res 32, 4776-4785.
Zhang, W., Dahlberg, J.E., and Tam, W. (2007). MicroRNAs in tumorigenesis: a primer. Am J Pathol 171, 728-738.
Ziche, M., Morbidelli, L., Choudhuri, R., Zhang, H.T., Donnini, S., Granger, H.J., and Bicknell, R. (1997). Nitric oxide synthase lies downstream from vascular endothelial growth factor-induced but not basic fibroblast growth factor-induced angiogenesis. J Clin Invest 99, 2625-2634.