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MicroRNA and AU-rich element regulation of prostaglandin synthesis

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Abstract

Many lines of evidence demonstrate that prostaglandins play an important role in cancer, and enhanced synthesis of prostaglandin E2 (PGE2) is often observed in various human malignancies often associated with poor prognosis. PGE2 synthesis is initiated with the release of arachidonic acid by phospholipase enzymes, where it is then converted into the intermediate prostaglandin prostaglandin H2 (PGH2) by members of the cyclooxygenase family. The synthesis of PGE2 from PGH2 is facilitated by three different PGE synthases, and functional PGE2 can promote tumor growth by binding to four EP receptors to activate signaling pathways that control cell proliferation, migration, apoptosis, and angiogenesis. An integral method of controlling gene expression is by posttranscriptional mechanisms that regulate mRNA stability and protein translation. Messenger RNA regulatory elements typically reside within the 3′ untranslated region (3′UTR) of the transcript and play a critical role in targeting specific mRNAs for posttranscriptional regulation through microRNA (miRNA) binding and adenylate- and uridylate-rich element RNA-binding proteins. In this review, we highlight the current advances in our understanding of the impact these RNA sequence elements have upon regulating PGE2 levels. We also identify various RNA sequence elements consistently observed within the 3′UTRs of the genes involved in the PGE2 pathway, indicating these binding sites for miRNAs and RNA-binding proteins to be central regulators of PGE2 synthesis and function. These findings may provide a rationale for the development of new therapeutic approaches to control tumor growth and metastasis promoted by elevated PGE2 levels.

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References

  1. Funk, C. D. (2001). Prostaglandins and leukotrienes: advances in eicosanoid biology. Science, 294(5548), 1871–1875.

    PubMed  CAS  Google Scholar 

  2. Wang, D., & Dubois, R. N. (2010). Eicosanoids and cancer. Nature Reviews Cancer, 10(3), 181–193.

    PubMed  CAS  Google Scholar 

  3. Legler, D. F., Bruckner, M., Uetz-von Allmen, E., & Krause, P. (2010). Prostaglandin E2 at new glance: novel insights in functional diversity offer therapeutic chances. International Journal of Biochemistry and Cell Biolgy, 42(2), 198–201.

    CAS  Google Scholar 

  4. Rigas, B., Goldman, I. S., & Levine, L. (1993). Altered eicosanoid levels in human colon cancer. The Journal of Laboratory and Clinical Medicine, 122(5), 518–523.

    PubMed  CAS  Google Scholar 

  5. McLemore, T. L., Hubbard, W. C., Litterst, C. L., Liu, M. C., Miller, S., McMahon, N. A., et al. (1988). Profiles of prostaglandin biosynthesis in normal lung and tumor tissue from lung cancer patients. Cancer Research, 48(11), 3140–3147.

    PubMed  CAS  Google Scholar 

  6. Hambek, M., Baghi, M., Wagenblast, J., Schmitt, J., Baumann, H., & Knecht, R. (2007). Inverse correlation between serum PGE2 and T classification in head and neck cancer. Head & Neck, 29(3), 244–248.

    Google Scholar 

  7. Cheadle, C., Fan, J., Cho-Chung, Y. S., Werner, T., Ray, J., Do, L., et al. (2005). Control of gene expression during T cell activation: alternate regulation of mRNA transcription and mRNA stability. BioMed Central Genomics, 6(1), 75.

    PubMed  Google Scholar 

  8. Garneau, N. L., Wilusz, J., & Wilusz, C. J. (2007). The highways and byways of mRNA decay. Nature Reviews Molecular Cell Biology, 8(2), 113–126.

    PubMed  CAS  Google Scholar 

  9. Fabian, M. R., Sonenberg, N., & Filipowicz, W. (2010). Regulation of mRNA translation and stability by microRNAs. Annual Review of Biochemistry, 79, 351–379.

    PubMed  CAS  Google Scholar 

  10. Friedman, R. C., Farh, K. K., Burge, C. B., & Bartel, D. P. (2009). Most mammalian mRNAs are conserved targets of microRNAs. Genome Research, 19(1), 92–105.

    PubMed  CAS  Google Scholar 

  11. von Roretz, C., & Gallouzi, I. E. (2008). Decoding ARE-mediated decay: is microRNA part of the equation? The Journal of Cell Biology, 181(2), 189–194.

    Google Scholar 

  12. Park, J. Y., Pillinger, M. H., & Abramson, S. B. (2006). Prostaglandin E2 synthesis and secretion: the role of PGE2 synthases. Clinical Immunology, 119(3), 229–240.

    PubMed  CAS  Google Scholar 

  13. Simmons, D. L., Botting, R. M., & Hla, T. (2004). Cyclooxygenase isozymes: the biology of prostaglandin synthesis and inhibition. Pharmacology Reviews, 56(3), 387–437.

    CAS  Google Scholar 

  14. Rebecchi, M. J., & Pentyala, S. N. (2000). Structure, function, and control of phosphoinositide-specific phospholipase C. Physiological Reviews, 80(4), 1291–1335.

    PubMed  CAS  Google Scholar 

  15. Tang, X., Edwards, E. M., Holmes, B. B., Falck, J. R., & Campbell, W. B. (2006). Role of phospholipase C and diacylglyceride lipase pathway in arachidonic acid release and acetylcholine-induced vascular relaxation in rabbit aorta. American Journal of Physiology-Heart and Circulatory Physiology, 290(1), H37–H45.

    PubMed  CAS  Google Scholar 

  16. Smith, W. L., DeWitt, D. L., & Garavito, R. M. (2000). Cyclooxygenases: structural, cellular, and molecular biology. Annual Review of Biochemistry, 69, 145–182.

    PubMed  CAS  Google Scholar 

  17. Wang, D., Wang, H., Shi, Q., Katkuri, S., Walhi, W., Desvergne, B., et al. (2004). Prostaglandin E(2) promotes colorectal adenoma growth via transactivation of the nuclear peroxisome proliferator-activated receptor delta. Cancer Cell, 6(3), 285–295.

    PubMed  CAS  Google Scholar 

  18. Hara, S., Kamei, D., Sasaki, Y., Tanemoto, A., Nakatani, Y., & Murakami, M. (2010). Prostaglandin E synthases: understanding their pathophysiological roles through mouse genetic models. Biochimie, 92(6), 651–659.

    PubMed  CAS  Google Scholar 

  19. Jakobsson, P. J., Thoren, S., Morgenstern, R., & Samuelsson, B. (1999). Identification of human prostaglandin E synthase: a microsomal, glutathione-dependent, inducible enzyme, constituting a potential novel drug target. Proceedings of the National Academy of Sciences USA, 96(13), 7220–7225.

    CAS  Google Scholar 

  20. Samuelsson, B., Morgenstern, R., & Jakobsson, P. J. (2007). Membrane prostaglandin E synthase-1: a novel therapeutic target. Pharmacological Reviews, 59(3), 207–224.

    PubMed  CAS  Google Scholar 

  21. Watanabe, K., Kurihara, K., & Suzuki, T. (1999). Purification and characterization of membrane-bound prostaglandin E synthase from bovine heart. Biochimica et Biophysica Acta, 1439(3), 406–414.

    PubMed  CAS  Google Scholar 

  22. Tanioka, T., Nakatani, Y., Semmyo, N., Murakami, M., & Kudo, I. (2000). Molecular identification of cytosolic prostaglandin E2 synthase that is functionally coupled with cyclooxygenase-1 in immediate prostaglandin E2 biosynthesis. The Journal of Biological Chemistry, 275(42), 32775–32782.

    PubMed  CAS  Google Scholar 

  23. Tai, H. H., Ensor, C. M., Tong, M., Zhou, H., & Yan, F. (2002). Prostaglandin catabolizing enzymes. Prostaglandins & Other Lipid Mediators, 68–69, 483–493.

    Google Scholar 

  24. Coggins, K. G., Latour, A., Nguyen, M. S., Audoly, L., Coffman, T. M., & Koller, B. H. (2002). Metabolism of PGE2 by prostaglandin dehydrogenase is essential for remodeling the ductus arteriosus. Nature Medicine, 8(2), 91–92.

    PubMed  CAS  Google Scholar 

  25. Yan, M., Rerko, R. M., Platzer, P., Dawson, D., Willis, J., Tong, M., et al. (2004). 15-Hydroxyprostaglandin dehydrogenase, a COX-2 oncogene antagonist, is a TGF-Beta-induced suppressor of human gastrointestinal cancers. Proceedings of the National Academy of Sciences USA, 101(50), 17468–17473.

    CAS  Google Scholar 

  26. Myung, S. J., Rerko, R. M., Yan, M., Platzer, P., Guda, K., Dotson, A., et al. (2006). 15-Hydroxyprostaglandin dehydrogenase is an in vivo suppressor of colon tumorigenesis. Proceedings of the National Academy of Sciences USA, 103(32), 12098–12102.

    CAS  Google Scholar 

  27. Ding, Y., Tong, M., Liu, S., Moscow, J. A., & Tai, H. H. (2005). Nad + −linked 15-hydroxyprostaglandin dehydrogenase (15-PGDH) behaves as a tumor suppressor in lung cancer. Carcinogenesis, 26(1), 65–72.

    PubMed  CAS  Google Scholar 

  28. Huang, G., Eisenberg, R., Yan, M., Monti, S., Lawrence, E., Fu, P., et al. (2008). 15-Hydroxyprostaglandin dehydrogenase is a target of hepatocyte nuclear factor 3beta and a tumor suppressor in lung cancer. Cancer Research, 68(13), 5040–5048.

    PubMed  CAS  Google Scholar 

  29. Backlund, M. G., Mann, J. R., Holla, V. R., Buchanan, F. G., Tai, H. H., Musiek, E. S., et al. (2005). 15-Hydroxyprostaglandin dehydrogenase is down-regulated in colorectal cancer. The Journal of Biological Chemistry, 280(5), 3217–3223.

    PubMed  CAS  Google Scholar 

  30. Wolf, I., O’Kelly, J., Rubinek, T., Tong, M., Nguyen, A., Lin, B. T., et al. (2006). 15-Hydroxyprostaglandin dehydrogenase is a tumor suppressor of human breast cancer. Cancer Research, 66(15), 7818–7823.

    PubMed  CAS  Google Scholar 

  31. Hughes, D., Otani, T., Yang, P., Newman, R. A., Yantiss, R. K., Altorki, N. K., et al. (2008). NAD+-dependent 15-hydroxyprostaglandin dehydrogenase regulates levels of bioactive lipids in non-small cell lung cancer. Cancer Prevention Research, 1(4), 241–249.

    PubMed  CAS  Google Scholar 

  32. Thiel, A., Ganesan, A., Mrena, J., Junnila, S., Nykanen, A., Hemmes, A., et al. (2009). 15-Hydroxyprostaglandin dehydrogenase is down-regulated in gastric cancer. Clinical Cancer Research, 15(14), 4572–4580.

    PubMed  CAS  Google Scholar 

  33. Backlund, M. G., Mann, J. R., Holla, V. R., Shi, Q., Daikoku, T., Dey, S. K., et al. (2008). Repression of 15-hydroxyprostaglandin dehydrogenase involves histone deacetylase 2 and snail in colorectal cancer. Cancer Research, 68(22), 9331–9337.

    PubMed  CAS  Google Scholar 

  34. Tong, M., Ding, Y., & Tai, H. H. (2006). Histone deacetylase inhibitors and transforming growth factor-beta induce 15-hydroxyprostaglandin dehydrogenase expression in human lung adenocarcinoma cells. Biochemical Pharmacology, 72(6), 701–709.

    PubMed  CAS  Google Scholar 

  35. Hull, M. A., Ko, S. C., & Hawcroft, G. (2004). Prostaglandin EP receptors: targets for treatment and prevention of colorectal cancer. Molecular Cancer Therapeutics, 3(8), 1031–1039.

    PubMed  CAS  Google Scholar 

  36. Bhattacharya, M., Peri, K. G., Almazan, G., Ribeiro-da-Silva, A., Shichi, H., Durocher, Y., et al. (1998). Nuclear localization of prostaglandin E2 receptors. Proceedings of the National Academy of Sciences USA, 95(26), 15792–15797.

    CAS  Google Scholar 

  37. Breyer, M. D., & Breyer, R. M. (2000). Prostaglandin E receptors and the kidney. American Journal of Physiology. Renal Physiology, 279(1), F12–F23.

    PubMed  CAS  Google Scholar 

  38. Breyer, R. M., Bagdassarian, C. K., Myers, S. A., & Breyer, M. D. (2001). Prostanoid receptors: subtypes and signaling. Annual Review of Pharmacology and Toxicology, 41, 661–690.

    PubMed  CAS  Google Scholar 

  39. Sugimoto, Y., & Narumiya, S. (2007). Prostaglandin E receptors. The Journal of Biological Chemistry, 282(16), 11613–11617.

    PubMed  CAS  Google Scholar 

  40. Katoh, H., Watabe, A., Sugimoto, Y., Ichikawa, A., & Negishi, M. (1995). Characterization of the signal transduction of prostaglandin E receptor EP1 subtype in cDNA-transfected chinese hamster ovary cells. Biochimica et Biophysica Acta, 1244(1), 41–48.

    PubMed  Google Scholar 

  41. Fukuda, R., Kelly, B., & Semenza, G. L. (2003). Vascular endothelial growth factor gene expression in colon cancer cells exposed to prostaglandin E2 is mediated by hypoxia-inducible factor 1. Cancer Research, 63(9), 2330–2334.

    PubMed  CAS  Google Scholar 

  42. Fujino, H., West, K. A., & Regan, J. W. (2002). Phosphorylation of glycogen synthase kinase-3 and stimulation of T-cell factor signaling following activation of EP2 and EP4 prostanoid receptors by prostaglandin E2. The Journal of Biological Chemistry, 277(4), 2614–2619.

    PubMed  CAS  Google Scholar 

  43. Namba, T., Sugimoto, Y., Negishi, M., Irie, A., Ushikubi, F., Kakizuka, A., et al. (1993). Alternative splicing of C-terminal tail of prostaglandin E receptor subtype EP3 determines G-protein specificity. Nature, 365(6442), 166–170.

    PubMed  CAS  Google Scholar 

  44. Kotani, M., Tanaka, I., Ogawa, Y., Usui, T., Tamura, N., Mori, K., et al. (1997). Structural organization of the human prostaglandin EP3 receptor subtype gene (PTGER3). Genomics, 40(3), 425–434.

    PubMed  CAS  Google Scholar 

  45. Kawamori, T., Uchiya, N., Nakatsugi, S., Watanabe, K., Ohuchida, S., Yamamoto, H., et al. (2001). Chemopreventive effects of ONO-8711, a selective prostaglandin E receptor EP(1) antagonist, on breast cancer development. Carcinogenesis, 22(12), 2001–2004.

    PubMed  CAS  Google Scholar 

  46. Yang, L., Huang, Y., Porta, R., Yanagisawa, K., Gonzalez, A., Segi, E., et al. (2006). Host and direct antitumor effects and profound reduction in tumor metastasis with selective EP4 receptor antagonism. Cancer Research, 66(19), 9665–9672.

    PubMed  CAS  Google Scholar 

  47. Keith, R. L., Geraci, M. W., Nana-Sinkam, S. P., Breyer, R. M., Hudish, T. M., Meyer, A. M., et al. (2006). Prostaglandin E2 receptor subtype 2 (EP2) null mice are protected against murine lung tumorigenesis. Anticancer Research, 26(4B), 2857–2861.

    PubMed  CAS  Google Scholar 

  48. Guo, H., Ingolia, N. T., Weissman, J. S., & Bartel, D. P. (2010). Mammalian microRNAs predominantly act to decrease target mRNA levels. Nature, 466(7308), 835–840.

    PubMed  CAS  Google Scholar 

  49. Filipowicz, W., Bhattacharyya, S. N., & Sonenberg, N. (2008). Mechanisms of post-transcriptional regulation by microRNAs: are the answers in sight? Nature Reviews Genetics, 9(2), 102–114.

    PubMed  CAS  Google Scholar 

  50. Brennecke, J., Stark, A., Russell, R. B., & Cohen, S. M. (2005). Principles of microRNA-target recognition. PLoS Biology, 3(3), e85.

    PubMed  Google Scholar 

  51. Grimson, A., Farh, K. K., Johnston, W. K., Garrett-Engele, P., Lim, L. P., & Bartel, D. P. (2007). MicroRNA targeting specificity in mammals: determinants beyond seed pairing. Molecular Cell, 27(1), 91–105.

    PubMed  CAS  Google Scholar 

  52. Shin, C., Nam, J. W., Farh, K. K., Chiang, H. R., Shkumatava, A., & Bartel, D. P. (2010). Expanding the microRNA targeting code: functional sites with centered pairing. Molecular Cell, 38(6), 789–802.

    PubMed  CAS  Google Scholar 

  53. Cullen, B. R. (2004). Transcription and processing of human microRNA precursors. Molecular Cell, 16(6), 861–865.

    PubMed  CAS  Google Scholar 

  54. Altuvia, Y., Landgraf, P., Lithwick, G., Elefant, N., Pfeffer, S., Aravin, A., et al. (2005). Clustering and conservation patterns of human microRNAs. Nucleic Acids Research, 33(8), 2697–2706.

    PubMed  CAS  Google Scholar 

  55. Yu, J., Wang, F., Yang, G. H., Wang, F. L., Ma, Y. N., Du, Z. W., et al. (2006). Human microRNA clusters: genomic organization and expression profile in leukemia cell lines. Biochemical and Biophysical Research Communications, 349(1), 59–68.

    PubMed  CAS  Google Scholar 

  56. Griffiths-Jones, S., Saini, H. K., van Dongen, S., & Enright, A. J. (2008). MiRBase: tools for microRNA genomics. Nucleic Acids Research, 36, D154–D158. Database issue.

    PubMed  CAS  Google Scholar 

  57. He, L., & Hannon, G. J. (2004). MicroRNAs: small RNAs with a big role in gene regulation. Nature Reviews Genetics, 5(7), 522–531.

    PubMed  CAS  Google Scholar 

  58. Calin, G. A., & Croce, C. M. (2006). MicroRNA signatures in human cancers. Nature Reviews. Cancer, 6(11), 857–866.

    PubMed  CAS  Google Scholar 

  59. Croce, C. M. (2009). Causes and consequences of microRNA dysregulation in cancer. Nature Reviews Genetics, 10(10), 704–714.

    PubMed  CAS  Google Scholar 

  60. Ryan, B. M., Robles, A. I., & Harris, C. C. (2010). Genetic variation in microRNA networks: the implications for cancer research. Nature Reviews. Cancer, 10(6), 389–402.

    PubMed  CAS  Google Scholar 

  61. Lu, J., Getz, G., Miska, E. A., Alvarez-Saavedra, E., Lamb, J., Peck, D., et al. (2005). MicroRNA expression profiles classify human cancers. Nature, 435(7043), 834–838.

    PubMed  CAS  Google Scholar 

  62. Calin, G. A., Dumitru, C. D., Shimizu, M., Bichi, R., Zupo, S., Noch, E., et al. (2002). Frequent deletions and down-regulation of micro- RNA genes miR15 and miR16 at 13q14 in chronic lymphocytic leukemia. Proceedings of the National Academy of Sciences USA, 99(24), 15524–15529.

    CAS  Google Scholar 

  63. Calin, G. A., Cimmino, A., Fabbri, M., Ferracin, M., Wojcik, S. E., Shimizu, M., et al. (2008). MiR-15a and miR-16-1 cluster functions in human leukemia. Proceedings of the National Academy of Sciences USA, 105(13), 5166–5171.

    CAS  Google Scholar 

  64. Chang, T. C., Yu, D., Lee, Y. S., Wentzel, E. A., Arking, D. E., West, K. M., et al. (2008). Widespread microRNA repression by Myc contributes to tumorigenesis. Nature Genetics, 40(1), 43–50.

    PubMed  CAS  Google Scholar 

  65. Suzuki, H. I., Yamagata, K., Sugimoto, K., Iwamoto, T., Kato, S., & Miyazono, K. (2009). Modulation of microRNA processing by p53. Nature, 460(7254), 529–533.

    PubMed  CAS  Google Scholar 

  66. Lewis, B. P., Shih, I. H., Jones-Rhoades, M. W., Bartel, D. P., & Burge, C. B. (2003). Prediction of mammalian microRNA targets. Cell, 115(7), 787–798.

    PubMed  CAS  Google Scholar 

  67. Esquela-Kerscher, A., & Slack, F. J. (2006). Oncomirs—microRNAs with a role in cancer. Nature Reviews. Cancer, 6(4), 259–269.

    PubMed  CAS  Google Scholar 

  68. Rehmsmeier, M., Steffen, P., Hochsmann, M., & Giegerich, R. (2004). Fast and effective prediction of microRNA/target duplexes. RNA, 10(10), 1507–1517.

    PubMed  CAS  Google Scholar 

  69. Kruger, J., & Rehmsmeier, M. (2006). RNAhybrid: microRNA target prediction easy, fast and flexible. Nucleic Acids Research, 34(suppl 2), W451–W454.

    PubMed  Google Scholar 

  70. Betel, D., Wilson, M., Gabow, A., Marks, D. S., & Sander, C. (2008). The microRNA.org resource targets and expression. Nucleic Acids Research, 36, D149–D153. Database issue.

    PubMed  CAS  Google Scholar 

  71. Griffiths-Jones, S., Grocock, R. J., van Dongen, S., Bateman, A., & Enright, A. J. (2006). MiRBase: microRNA sequences, targets and gene nomenclature. Nucleic Acids Research, 34, D140–D144. Database issue.

    PubMed  CAS  Google Scholar 

  72. Mongroo, P. S., & Rustgi, A. K. (2010). The role of the miR-200 family in epithelial-mesenchymal transition. Cancer Biology & Therapy, 10(3), 219–222.

    CAS  Google Scholar 

  73. Sato, Y., Kobayashi, H., Suto, Y., Olney, H. J., Davis, E. M., Super, H. G., et al. (2001). Chromosomal instability in chromosome band 12p13: multiple breaks leading to complex rearrangements including cytogenetically undetectable sub-clones. Leukemia, 15(8), 1193–1202.

    PubMed  CAS  Google Scholar 

  74. Bagchi, A., & Mills, A. A. (2008). The quest for the 1p36 tumor suppressor. Cancer Research, 68(8), 2551–2556.

    PubMed  CAS  Google Scholar 

  75. Vrba, L., Jensen, T. J., Garbe, J. C., Heimark, R. L., Cress, A. E., Dickinson, S., et al. (2010). Role for DNA methylation in the regulation of miR-200c and miR-141 expression in normal and cancer cells. PloS One, 5(1), e8697.

    PubMed  Google Scholar 

  76. Gregory, P. A., Bert, A. G., Paterson, E. L., Barry, S. C., Tsykin, A., Farshid, G., et al. (2008). The miR-200 family and miR-205 regulate epithelial to mesenchymal transition by targeting ZEB1 and SIP1. Nature Cell Biology, 10(5), 593–601.

    PubMed  CAS  Google Scholar 

  77. Pang, Y., Young, C. Y., & Yuan, H. (2010). MicroRNAs and prostate cancer. Acta Biochimica et Biophysica Sinica, 42(6), 363–369.

    PubMed  CAS  Google Scholar 

  78. Gibbons, D. L., Lin, W., Creighton, C. J., Rizvi, Z. H., Gregory, P. A., Goodall, G. J., et al. (2009). Contextual extracellular cues promote tumor cell EMT and metastasis by regulating miR-200 family expression. Genes & Development, 23(18), 2140–2151.

    CAS  Google Scholar 

  79. Saydam, O., Shen, Y., Wurdinger, T., Senol, O., Boke, E., James, M. F., et al. (2009). Downregulated microRNA-200a in meningiomas promotes tumor growth by reducing E-cadherin and activating the Wnt/beta-catenin signaling pathway. Molecular and Cellular Biology, 29(21), 5923–5940.

    PubMed  CAS  Google Scholar 

  80. Korpal, M., Lee, E. S., Hu, G., & Kang, Y. (2008). The miR-200 family inhibits epithelial-mesenchymal transition and cancer cell migration by direct targeting of E-cadherin transcriptional repressors ZEB1 and ZEB2. The Journal of Biological Chemistry, 283(22), 14910–14914.

    PubMed  CAS  Google Scholar 

  81. Spaderna, S., Schmalhofer, O., Wahlbuhl, M., Dimmler, A., Bauer, K., Sultan, A., et al. (2008). The transcriptional repressor ZEB1 promotes metastasis and loss of cell polarity in cancer. Cancer Research, 68(2), 537–544.

    PubMed  CAS  Google Scholar 

  82. Uhlmann, S., Zhang, J. D., Schwager, A., Mannsperger, H., Riazalhosseini, Y., Burmester, S., et al. (2010). MiR-200bc/429 cluster targets PLCgamma1 and differentially regulates proliferation and EGF-driven invasion than miR-200a/141 in breast cancer. Oncogene, 29(30), 4297–4306.

    PubMed  CAS  Google Scholar 

  83. Buchanan, F. G., Wang, D., Bargiacchi, F., & DuBois, R. N. (2003). Prostaglandin E2 regulates cell migration via the intracellular activation of the epidermal growth factor receptor. The Journal of Biological Chemistry, 278(37), 35451–35457.

    PubMed  CAS  Google Scholar 

  84. Adam, L., Zhong, M., Choi, W., Qi, W., Nicoloso, M., Arora, A., et al. (2009). MiR-200 expression regulates epithelial-to-mesenchymal transition in bladder cancer cells and reverses resistance to epidermal growth factor receptor therapy. Clinical Cancer Research, 15(16), 5060–5072.

    PubMed  CAS  Google Scholar 

  85. Xu, N., Papagiannakopoulos, T., Pan, G., Thomson, J. A., & Kosik, K. S. (2009). MicroRNA-145 regulates OCT4, SOX2, and KLF4 and represses pluripotency in human embryonic stem cells. Cell, 137(4), 647–658.

    PubMed  CAS  Google Scholar 

  86. Cordes, K. R., Sheehy, N. T., White, M. P., Berry, E. C., Morton, S. U., Muth, A. N., et al. (2009). MiR-145 and miR-143 regulate smooth muscle cell fate and plasticity. Nature, 460(7256), 705–710.

    PubMed  CAS  Google Scholar 

  87. Zhang, X., Liu, S., Hu, T., He, Y., & Sun, S. (2009). Up-regulated microRNA-143 transcribed by nuclear factor kappa B enhances hepatocarcinoma metastasis by repressing fibronectin expression. Hepatology, 50(2), 490–499.

    PubMed  CAS  Google Scholar 

  88. Wu, B. L., Xu, L. Y., Du, Z. P., Liao, L. D., Zhang, H. F., Huang, Q., et al. (2011). MiRNA profile in esophageal squamous cell carcinoma: downregulation of miR-143 and miR-145. World Journal of Gastroenterology, 17(1), 79–88.

    PubMed  CAS  Google Scholar 

  89. Michael, M. Z., O’Connor, S. M., van Holst Pellekaan, N. G., Young, G. P., & James, R. J. (2003). Reduced accumulation of specific microRNAs in colorectal neoplasia. Molecular Cancer Research, 1(12), 882–891.

    PubMed  CAS  Google Scholar 

  90. Akao, Y., Nakagawa, Y., & Naoe, T. (2006). MicroRNAs 143 and 145 are possible common onco-microRNAs in human cancers. Oncology Reports, 16(4), 845–850.

    PubMed  CAS  Google Scholar 

  91. Bandres, E., Cubedo, E., Agirre, X., Malumbres, R., Zarate, R., Ramirez, N., et al. (2006). Identification by real-time PCR of 13 mature microRNAs differentially expressed in colorectal cancer and non-tumoral tissues. Molecular Cancer, 5, 29.

    PubMed  CAS  Google Scholar 

  92. Slaby, O., Svoboda, M., Fabian, P., Smerdova, T., Knoflickova, D., Bednarikova, M., et al. (2007). Altered expression of miR-21, miR-31, miR-143 and miR-145 is related to clinicopathologic features of colorectal cancer. Oncology, 72(5–6), 397–402.

    PubMed  CAS  Google Scholar 

  93. Wach, S., Nolte, E., Szczyrba, J., Stohr, R., Hartmann, A., Orntoft, T., et al. (2011). MiRNA profiles of prostate carcinoma detected by multi-platform miRNA screening. International Journal of Cancer. doi:10.1002/ijc.26064.

  94. Zhang, H., Cai, X., Wang, Y., Tang, H., Tong, D., & Ji, F. (2010). MicroRNA-143, down-regulated in osteosarcoma, promotes apoptosis and suppresses tumorigenicity by targeting Bcl-2. Oncology Reports, 24(5), 1363–1369.

    PubMed  CAS  Google Scholar 

  95. Song, T., Xia, W., Shao, N., Zhang, X., Wang, C., Wu, Y., et al. (2010). Differential miRNA expression profiles in bladder urothelial carcinomas. Asian Pacific Journal of Cancer Prevention, 11(4), 905–911.

    PubMed  Google Scholar 

  96. Akao, Y., Nakagawa, Y., Kitade, Y., Kinoshita, T., & Naoe, T. (2007). Downregulation of microRNAs-143 and -145 in B-cell malignancies. Cancer Science, 98(12), 1914–1920.

    PubMed  CAS  Google Scholar 

  97. Takagi, T., Iio, A., Nakagawa, Y., Naoe, T., Tanigawa, N., & Akao, Y. (2009). Decreased expression of microRNA-143 and -145 in human gastric cancers. Oncology, 77(1), 12–21.

    PubMed  CAS  Google Scholar 

  98. Sachdeva, M., Zhu, S., Wu, F., Wu, H., Walia, V., Kumar, S., et al. (2009). P53 represses c-Myc through induction of the tumor suppressor miR-145. Proceedings of the National Academy of Sciences USA, 106(9), 3207–3212.

    CAS  Google Scholar 

  99. Chen, X., Guo, X., Zhang, H., Xiang, Y., Chen, J., Yin, Y., et al. (2009). Role of miR-143 targeting KRAS in colorectal tumorigenesis. Oncogene, 28(10), 1385–1392.

    PubMed  CAS  Google Scholar 

  100. Shi, B., Sepp-Lorenzino, L., Prisco, M., Linsley, P., deAngelis, T., & Baserga, R. (2007). Micro RNA 145 targets the insulin receptor substrate-1 and inhibits the growth of colon cancer cells. The Journal of Biological Chemistry, 282(45), 32582–32590.

    PubMed  CAS  Google Scholar 

  101. Akao, Y., Nakagawa, Y., Iio, A., & Naoe, T. (2009). Role of microRNA-143 in Fas-mediated apoptosis in human T-cell leukemia Jurkat cells. Leukemia Research, 33(11), 1530–1538.

    PubMed  CAS  Google Scholar 

  102. Tai, M. H., Chang, C. C., Kiupel, M., Webster, J. D., Olson, L. K., & Trosko, J. E. (2005). Oct4 expression in adult human stem cells: evidence in support of the stem cell theory of carcinogenesis. Carcinogenesis, 26(2), 495–502.

    PubMed  CAS  Google Scholar 

  103. Wu, Y., Liu, S., Xin, H., Jiang, J., Younglai, E., Sun, S., et al. (2011). Up-regulation of microRNA-145 promotes differentiation by repressing OCT4 in human endometrial adenocarcinoma cells. Cancer, 1(1), 1–10.

    Google Scholar 

  104. Boultwood, J., Pellagatti, A., McKenzie, A. N., & Wainscoat, J. S. (2010). Advances in the 5q- syndrome. Blood, 116(26), 5803–5811.

    PubMed  CAS  Google Scholar 

  105. Starczynowski, D. T., Kuchenbauer, F., Argiropoulos, B., Sung, S., Morin, R., Muranyi, A., et al. (2010). Identification of miR-145 and miR-146a as mediators of the 5q- syndrome phenotype. Nature Medicine, 16(1), 49–58.

    PubMed  CAS  Google Scholar 

  106. Elia, L., Quintavalle, M., Zhang, J., Contu, R., Cossu, L., Latronico, M. V., et al. (2009). The knockout of miR-143 and -145 alters smooth muscle cell maintenance and vascular homeostasis in mice: correlates with human disease. Cell Death and Differentiation, 16(12), 1590–1598.

    PubMed  CAS  Google Scholar 

  107. Yau, L., & Zahradka, P. (2003). PGE(2) stimulates vascular smooth muscle cell proliferation via the EP2 receptor. Molecular and Cellular Endocrinology, 203(1–2), 77–90.

    PubMed  CAS  Google Scholar 

  108. Varambally, S., Cao, Q., Mani, R. S., Shankar, S., Wang, X., Ateeq, B., et al. (2008). Genomic loss of microRNA-101 leads to overexpression of histone methyltransferase EZH2 in cancer. Science, 322(5908), 1695–1699.

    PubMed  CAS  Google Scholar 

  109. Strillacci, A., Griffoni, C., Sansone, P., Paterini, P., Piazzi, G., Lazzarini, G., et al. (2009). MiR-101 downregulation is involved in cyclooxygenase-2 overexpression in human colon cancer cells. Experimental Cell Research, 315(8), 1439–1447.

    PubMed  CAS  Google Scholar 

  110. Zhang, J. G., Guo, J. F., Liu, D. L., Liu, Q., & Wang, J. J. (2011). MicroRNA-101 exerts tumor-suppressive functions in non-small cell lung cancer through directly targeting enhancer of zeste homolog 2. Journal of Thoracic Oncology, 6(4), 671–678.

    PubMed  Google Scholar 

  111. Smits, M., Nilsson, J., Mir, S. E., van der Stoop, P. M., Hulleman, E., Niers, J. M., et al. (2010). MiR-101 is down-regulated in glioblastoma resulting in EZH2-induced proliferation, migration, and angiogenesis. Oncotarget, 1(8), 710–720.

    PubMed  Google Scholar 

  112. Su, H., Yang, J. R., Xu, T., Huang, J., Xu, L., Yuan, Y., et al. (2009). MicroRNA-101, down-regulated in hepatocellular carcinoma, promotes apoptosis and suppresses tumorigenicity. Cancer Research, 69(3), 1135–1142.

    PubMed  CAS  Google Scholar 

  113. Friedman, J. M., Liang, G., Liu, C. C., Wolff, E. M., Tsai, Y. C., Ye, W., et al. (2009). The putative tumor suppressor microRNA-101 modulates the cancer epigenome by repressing the polycomb group protein EZH2. Cancer Research, 69(6), 2623–2629.

    PubMed  CAS  Google Scholar 

  114. Wang, H. J., Ruan, H. J., He, X. J., Ma, Y. Y., Jiang, X. T., Xia, Y. J., et al. (2010). MicroRNA-101 is down-regulated in gastric cancer and involved in cell migration and invasion. European Journal of Cancer, 46(12), 2295–2303.

    PubMed  CAS  Google Scholar 

  115. Chakrabarty, A., Tranguch, S., Daikoku, T., Jensen, K., Furneaux, H., & Dey, S. K. (2007). MicroRNA regulation of cyclooxygenase-2 during embryo implantation. Proceedings of the National Academy of Sciences USA, 104(38), 15144–15149.

    CAS  Google Scholar 

  116. Daikoku, T., Hirota, Y., Tranguch, S., Joshi, A. R., DeMayo, F. J., Lydon, J. P., et al. (2008). Conditional loss of uterine Pten unfailingly and rapidly induces endometrial cancer in mice. Cancer Research, 68(14), 5619–5627.

    PubMed  CAS  Google Scholar 

  117. Wang, D., & Dubois, R. N. (2010). The role of COX-2 in intestinal inflammation and colorectal cancer. Oncogene, 29(6), 781–788.

    PubMed  CAS  Google Scholar 

  118. Tsujii, M., Kawano, S., Tsuji, S., Sawaoka, H., Hori, M., & DuBois, R. N. (1998). Cyclooxygenase regulates angiogenesis induced by colon cancer cells. Cell, 93(5), 705–716.

    PubMed  CAS  Google Scholar 

  119. Dohner, H., Stilgenbauer, S., Benner, A., Leupolt, E., Krober, A., Bullinger, L., et al. (2000). Genomic aberrations and survival in chronic lymphocytic leukemia. The New England Journal of Medicine, 343(26), 1910–1916.

    PubMed  CAS  Google Scholar 

  120. Klein, U., Lia, M., Crespo, M., Siegel, R., Shen, Q., Mo, T., et al. (2010). The DLEU2/miR-15a/16-1 cluster controls B cell proliferation and its deletion leads to chronic lymphocytic leukemia. Cancer Cell, 17(1), 28–40.

    PubMed  CAS  Google Scholar 

  121. Sanchez-Beato, M., Sanchez-Aguilera, A., & Piris, M. A. (2003). Cell cycle deregulation in B-cell lymphomas. Blood, 101(4), 1220–1235.

    PubMed  CAS  Google Scholar 

  122. Cimmino, A., Calin, G. A., Fabbri, M., Iorio, M. V., Ferracin, M., Shimizu, M., et al. (2005). MiR-15 and miR-16 induce apoptosis by targeting BCL2. Proceedings of the National Academy of Sciences USA, 102(39), 13944–13949.

    CAS  Google Scholar 

  123. Liu, Q., Fu, H., Sun, F., Zhang, H., Tie, Y., Zhu, J., et al. (2008). MiR-16 family induces cell cycle arrest by regulating multiple cell cycle genes. Nucleic Acids Research, 36(16), 5391–5404.

    PubMed  CAS  Google Scholar 

  124. Cummins, J. M., He, Y., Leary, R. J., Pagliarini, R., Diaz, L. A., Jr., Sjoblom, T., et al. (2006). The colorectal microRNAome. Proceedings of the National Academy of Sciences USA, 103(10), 3687–3692.

    CAS  Google Scholar 

  125. Bottoni, A., Piccin, D., Tagliati, F., Luchin, A., Zatelli, M. C., & Degli Uberti, E. C. (2005). MiR-15a and miR-16-1 down-regulation in pituitary adenomas. Journal of Cellular Physiology, 204(1), 280–285.

    PubMed  CAS  Google Scholar 

  126. Bonci, D., Coppola, V., Musumeci, M., Addario, A., Giuffrida, R., Memeo, L., et al. (2008). The miR-15a-miR-16-1 cluster controls prostate cancer by targeting multiple oncogenic activities. Nature Medicine, 14(11), 1271–1277.

    PubMed  CAS  Google Scholar 

  127. Navarro, A., Diaz, T., Gallardo, E., Vinolas, N., Marrades, R. M., Gel, B., et al. (2011). Prognostic implications of miR-16 expression levels in resected non-small-cell lung cancer. Journal of Surgical Oncology, 103(5), 411–415.

    PubMed  CAS  Google Scholar 

  128. Lopez de Silanes, I., Quesada, M. P., & Esteller, M. (2007). Aberrant regulation of messenger RNA 3′-untranslated region in human cancer. Cellular Oncology, 29(1), 1–17.

    PubMed  CAS  Google Scholar 

  129. Jing, Q., Huang, S., Guth, S., Zarubin, T., Motoyama, A., Chen, J., et al. (2005). Involvement of microRNA in AU-rich element-mediated mRNA instability. Cell, 120(5), 623–634.

    PubMed  CAS  Google Scholar 

  130. Shanmugam, N., Reddy, M. A., & Natarajan, R. (2008). Distinct roles of heterogeneous nuclear ribonuclear protein K and microRNA-16 in cyclooxygenase-2 RNA stability induced by S100b, a ligand of the receptor for advanced glycation end products. The Journal of Biological Chemistry, 283(52), 36221–36233.

    PubMed  CAS  Google Scholar 

  131. Xu, F., Zhang, X., Lei, Y., Liu, X., Liu, Z., Tong, T., et al. (2010). Loss of repression of HuR translation by miR-16 may be responsible for the elevation of HuR in human breast carcinoma. Journal of Cellular Biochemistry, 111(3), 727–734.

    PubMed  CAS  Google Scholar 

  132. Pan, X., Wang, Z. X., & Wang, R. (2011). MicroRNA-21: a novel therapeutic target in human cancer. Cancer Biology & Therapy, 10(12), 1224–1232.

    Google Scholar 

  133. Volinia, S., Calin, G. A., Liu, C. G., Ambs, S., Cimmino, A., Petrocca, F., et al. (2006). A microRNA expression signature of human solid tumors defines cancer gene targets. Proceedings of the National Academy of Sciences USA, 103(7), 2257–2261.

    CAS  Google Scholar 

  134. Markou, A., Tsaroucha, E. G., Kaklamanis, L., Fotinou, M., Georgoulias, V., & Lianidou, E. S. (2008). Prognostic value of mature microRNA-21 and microRNA-205 overexpression in non-small cell lung cancer by quantitative real-time RT-PCR. Clinical Chemistry Online, 54(10), 1696–1704.

    CAS  Google Scholar 

  135. Chan, S. H., Wu, C. W., Li, A. F., Chi, C. W., & Lin, W. C. (2008). MiR-21 microRNA expression in human gastric carcinomas and its clinical association. Anticancer Research, 28(2A), 907–911.

    PubMed  Google Scholar 

  136. Gao, W., Shen, H., Liu, L., Xu, J., & Shu, Y. (2011). MiR-21 overexpression in human primary squamous cell lung carcinoma is associated with poor patient prognosis. Journal of Cancer Research and Clinical Oncology, 137(4), 557–566.

    PubMed  CAS  Google Scholar 

  137. Yanaihara, N., Caplen, N., Bowman, E., Seike, M., Kumamoto, K., Yi, M., et al. (2006). Unique microRNA molecular profiles in lung cancer diagnosis and prognosis. Cancer Cell, 9(3), 189–198.

    PubMed  CAS  Google Scholar 

  138. Newbury, S. F., Muhlemann, O., & Stoecklin, G. (2006). Turnover in the alps: an mRNA perspective. Workshops on mechanisms and regulation of mRNA turnover. European Molecular Biology Organization Reports, 7(2), 143–148.

    PubMed  CAS  Google Scholar 

  139. Eulalio, A., Behm-Ansmant, I., & Izaurralde, E. (2007). P bodies: at the crossroads of post-transcriptional pathways. Nature Reviews Molecular Cell Biology, 8(1), 9–22.

    PubMed  CAS  Google Scholar 

  140. Anderson, P., & Kedersha, N. (2008). Stress granules: the tao of RNA triage. Trends in Biochemical Sciences, 33(3), 141–150.

    PubMed  CAS  Google Scholar 

  141. Barreau, C., Paillard, L., & Osborne, H. B. (2005). AU-rich elements and associated factors: are there unifying principles? Nucleic Acids Research, 33(22), 7138–7150.

    PubMed  CAS  Google Scholar 

  142. Bakheet, T., Williams, B. R., & Khabar, K. S. (2006). Ared 3.0: the large and diverse AU-rich transcriptome. Nucleic Acids Research, 34, D111–D114. Database issue.

    PubMed  CAS  Google Scholar 

  143. Gruber, A. R., Fallmann, J., Kratochvill, F., Kovarik, P., & Hofacker, I. L. (2010). AREsite: a database for the comprehensive investigation of AU-rich elements. Nucleic Acids Research, 39, D66–D69. Database issue.

    PubMed  Google Scholar 

  144. Dixon, D. A. (2004). Dysregulated post-transcriptional control of COX-2 gene expression in cancer. Current Pharmaceutical Design, 10(6), 635–646.

    PubMed  CAS  Google Scholar 

  145. Young, L. E., & Dixon, D. A. (2010). Posttranscriptional regulation of cyclooxygenase 2 expression in colorectal cancer. Current Colorectal Cancer Reports, 6(2), 60–67.

    PubMed  Google Scholar 

  146. Dixon, D. A., Kaplan, C. D., McIntyre, T. M., Zimmerman, G. A., & Prescott, S. M. (2000). Post-transcriptional control of cyclooxygenase-2 gene expression. The role of the 3′-untranslated region. The Journal of Biological Chemistry, 275(16), 11750–11757.

    PubMed  CAS  Google Scholar 

  147. Dixon, D. A. (2003). Regulation of COX-2 expression in human cancer. Progress in Experimental Tumor Research, 37, 52–71.

    PubMed  CAS  Google Scholar 

  148. Tay, A., Maxwell, P., Li, Z. G., Goldberg, H., & Skorecki, K. (1994). Cytosolic phospholipase A2 gene expression in rat mesangial cells is regulated post-transcriptionally. The Biochemical Journal, 304(2), 417–422.

    PubMed  CAS  Google Scholar 

  149. Hack, N., Tay, A., Schultz, A., Muzin, N., Clayman, P., Egan, S., et al. (1996). Regulation of rat kidney mesangial cell phospholipase A2. Clinical and Experimental Pharmacology and Physiology, 23(1), 71–75.

    PubMed  CAS  Google Scholar 

  150. Lee, Y. H., Lee, H. J., Lee, S. J., Min, D. S., Baek, S. H., Kim, Y. S., et al. (1995). Down-regulation of phospholipase C-gamma 1 during the differentiation of U937 cells. Federation of European Biochemical Societies Letters, 358(2), 105–108.

    PubMed  CAS  Google Scholar 

  151. Brennan, C. M., & Steitz, J. A. (2001). HuR and mRNA stability. Cellular and Molecular Life Sciences, 58, 266–277.

    PubMed  CAS  Google Scholar 

  152. Dalmau, J., Furneaux, H. M., Rosenblum, M. K., Graus, F., & Posner, J. B. (1991). Detection of the anti-Hu antibody in specific regions of the nervous system and tumor from patients with paraneoplastic encephalomyelitis/sensory neuronopathy. Neurology, 41(11), 1757–1764.

    PubMed  CAS  Google Scholar 

  153. Voltz, R. (2002). Paraneoplastic neurological syndromes: an update on diagnosis, pathogenesis, and therapy. Lancet Neurology, 1(5), 294–305.

    PubMed  Google Scholar 

  154. Keene, J. (1999). Why is Hu where? Shuttling of early-response messenger RNA subsets. Proceedings of the National Academy of Sciences USA, 96(1), 5–7.

    CAS  Google Scholar 

  155. Ming, X. F., Stoecklin, G., Lu, M., Looser, R., & Moroni, C. (2001). Parallel and independent regulation of interleukin-3 mRNA turnover by phosphatidylinositol 3-kinase and p38 mitogen-activated protein kinase. Molecular and Cellular Biology, 21(17), 5778–5789.

    PubMed  CAS  Google Scholar 

  156. Briata, P., Ilengo, C., Corte, G., Moroni, C., Rosenfeld, M. G., Chen, C. Y., et al. (2003). The Wnt/beta-catenin→Pitx2 pathway controls the turnover of Pitx2 and other unstable mRNAs. Molecular Cell, 12(5), 1201–1211.

    PubMed  CAS  Google Scholar 

  157. Yang, X., Wang, W., Fan, J., Lal, A., Yang, D., Cheng, H., et al. (2004). Prostaglandin A2-mediated stabilization of p21 mRNA through an ERK-dependent pathway requiring the RNA-binding protein HuR. The Journal of Biological Chemistry, 279(47), 49298–49306.

    PubMed  CAS  Google Scholar 

  158. Meisner, N. C., Hintersteiner, M., Mueller, K., Bauer, R., Seifert, J. M., Naegeli, H. U., et al. (2007). Identification and mechanistic characterization of low-molecular-weight inhibitors for HuR. Nature Chemical Biology, 3(8), 508–515.

    PubMed  CAS  Google Scholar 

  159. Lopez de Silanes, I., Lal, A., & Gorospe, M. (2005). HuR: post-transcriptional paths to malignancy. RNA Biology, 2(1), 11–13.

    PubMed  CAS  Google Scholar 

  160. Abdelmohsen, K., & Gorospe, M. (2010). Posttranscriptional regulation of cancer traits by HuR. Wiley Interdisciplinary Reviews: RNA, 1, 214–229.

    PubMed  CAS  Google Scholar 

  161. Dixon, D. A., Tolley, N. D., King, P. H., Nabors, L. B., McIntyre, T. M., Zimmerman, G. A., et al. (2001). Altered expression of the mRNA stability factor HuR promotes cyclooxygenase-2 expression in colon cancer cells. The Journal of Clinical Investigation, 108(11), 1657–1665.

    PubMed  CAS  Google Scholar 

  162. Young, L. E., Sanduja, S., Bemis-Standoli, K., Pena, E. A., Price, R. L., & Dixon, D. A. (2009). The mRNA binding proteins HuR and tristetraprolin regulate cyclooxygenase 2 expression during colon carcinogenesis. Gastroenterology, 136(5), 1669–1679.

    PubMed  CAS  Google Scholar 

  163. Lopez de Silanes, I., Zhan, M., Lal, A., Yang, X., & Gorospe, M. (2004). Identification of a target RNA motif for RNA-binding protein HuR. Proceedings of the National Academy of Sciences USA, 101(9), 2987–2992.

    Google Scholar 

  164. Mukhopadhyay, D., Houchen, C. W., Kennedy, S., Dieckgraefe, B. K., & Anant, S. (2003). Coupled mRNA stabilization and translational silencing of cyclooxygenase-2 by a novel RNA binding protein, CUGBP2. Molecular Cell, 11(1), 113–126.

    PubMed  CAS  Google Scholar 

  165. Murmu, N., Jung, J., Mukhopadhyay, D., Houchen, C. W., Riehl, T. E., Stenson, W. F., et al. (2004). Dynamic antagonism between RNA-binding protein CUGBP2 and cyclooxygenase-2-mediated prostaglandin E2 in radiation damage. Proceedings of the National Academy of Sciences USA, 101(38), 13873–13878.

    CAS  Google Scholar 

  166. Sureban, S. M., Murmu, N., Rodriguez, P., May, R., Maheshwari, R., Dieckgraefe, B. K., et al. (2007). Functional antagonism between RNA binding proteins HuR and CUGBP2 determines the fate of COX-2 mRNA translation. Gastroenterology, 132(3), 1055–1065.

    PubMed  CAS  Google Scholar 

  167. Derry, J. M., Kerns, J. A., & Francke, U. (1995). RBM3, a novel human gene in Xp11.23 with a putative RNA-binding domain. Human Molecular Genetics, 4(12), 2307–2311.

    PubMed  CAS  Google Scholar 

  168. Dresios, J., Aschrafi, A., Owens, G. C., Vanderklish, P. W., Edelman, G. M., & Mauro, V. P. (2005). Cold stress-induced protein Rbm3 binds 60S ribosomal subunits, alters microRNA levels, and enhances global protein synthesis. Proceedings of the National Academy of Sciences USA, 102(6), 1865–1870.

    CAS  Google Scholar 

  169. Cok, S. J., & Morrison, A. R. (2001). The 3′-untranslated region of murine cyclooxygenase-2 contains multiple regulatory elements that alter message stability and translational efficiency. The Journal of Biological Chemistry, 276(25), 23179–23185.

    PubMed  CAS  Google Scholar 

  170. Anant, S., Houchen, C. W., Pawar, V., & Ramalingam, S. (2010). Role of RNA-binding proteins in colorectal carcinogenesis. Current Colorectal Cancer Reports, 6(2), 68–73.

    PubMed  Google Scholar 

  171. Sureban, S. M., Ramalingam, S., Natarajan, G., May, R., Subramaniam, D., Bishnupuri, K. S., et al. (2008). Translation regulatory factor RBM3 is a proto-oncogene that prevents mitotic catastrophe. Oncogene, 27(33), 4544–4556.

    PubMed  CAS  Google Scholar 

  172. Baou, M., Jewell, A., & Murphy, J. J. (2009). TIS11 family proteins and their roles in posttranscriptional gene regulation. Journal of Biomedicine and Biotechnology, 2009, 634520.

    PubMed  Google Scholar 

  173. Sanduja, S., Blanco, F. F., & Dixon, D. A. (2010). The roles of TTP and BRF proteins in regulated mRNA decay. Wiley Interdisciplinary Reviews. RNA, 2(1), 42–57.

    Google Scholar 

  174. Carballo, E., Lai, W. S., & Blackshear, P. J. (1998). Feedback inhibition of macrophage tumor necrosis factor-α production by tristetraprolin. Science, 281(5379), 1001–1005.

    PubMed  CAS  Google Scholar 

  175. Carballo, E., Lai, W. S., & Blackshear, P. J. (2000). Evidence that tristetraprolin is a physiological regulator of granulocyte-macrophage colony-stimulating factor messenger RNA deadenylation and stability. Blood, 95(6), 1891–1899.

    PubMed  CAS  Google Scholar 

  176. Chen, C. Y., Gherzi, R., Ong, S. E., Chan, E. L., Raijmakers, R., Pruijn, G. J., et al. (2001). AU binding proteins recruit the exosome to degrade ARE-containing mRNAs. Cell, 107(4), 451–464.

    PubMed  CAS  Google Scholar 

  177. Mukherjee, D., Gao, M., O’Connor, J. P., Raijmakers, R., Pruijn, G., Lutz, C. S., et al. (2002). The mammalian exosome mediates the efficient degradation of mRNAs that contain AU-rich elements. EMBO Journal, 21(1–2), 165–174.

    PubMed  CAS  Google Scholar 

  178. Fenger-Gron, M., Fillman, C., Norrild, B., & Lykke-Andersen, J. (2005). Multiple processing body factors and the ARE binding protein TTP activate mRNA decapping. Molecular Cell, 20(6), 905–915.

    PubMed  CAS  Google Scholar 

  179. Lykke-Andersen, J., & Wagner, E. (2005). Recruitment and activation of mRNA decay enzymes by two ARE-mediated decay activation domains in the proteins TTP and BRF-1. Genes & Development, 19(3), 351–361.

    CAS  Google Scholar 

  180. Hau, H. H., Walsh, R. J., Ogilvie, R. L., Williams, D. A., Reilly, C. S., & Bohjanen, P. R. (2007). Tristetraprolin recruits functional mRNA decay complexes to ARE sequences. Journal of Cellular Biochemistry, 100(6), 1477–1492.

    PubMed  CAS  Google Scholar 

  181. Kedersha, N., Stoecklin, G., Ayodele, M., Yacono, P., Lykke-Andersen, J., Fritzler, M. J., et al. (2005). Stress granules and processing bodies are dynamically linked sites of mRNP remodeling. The Journal of Cell Biology, 169(6), 871–884.

    PubMed  CAS  Google Scholar 

  182. Franks, T. M., & Lykke-Andersen, J. (2007). TTP and BRF proteins nucleate processing body formation to silence mRNAs with AU-rich elements. Genes & Development, 21(6), 719–735.

    CAS  Google Scholar 

  183. Taylor, G. A., Carballo, E., Lee, D. M., Lai, W. S., Thompson, M. J., Patel, D. D., et al. (1996). A pathogenetic role for TNF alpha in the syndrome of cachexia, arthritis, and autoimmunity resulting from tristetraprolin (TTP) deficiency. Immunity, 4(5), 445–454.

    PubMed  CAS  Google Scholar 

  184. Lai, W. S., Carballo, E., Strum, J. R., Kennington, E. A., Phillips, R. S., & Blackshear, P. J. (1999). Evidence that tristetraprolin binds to AU-rich elements and promotes the deadenylation and destabilization of tumor necrosis factor alpha mRNA. Molecular and Cellular Biology, 19(6), 4311–4323.

    PubMed  CAS  Google Scholar 

  185. Sawaoka, H., Dixon, D. A., Oates, J. A., & Boutaud, O. (2003). Tristetrapolin binds to the 3′ untranslated region of cyclooxygenase-2 mRNA: a polyadenylation variant in a cancer cell line lacks the binding site. The Journal of Biological Chemistry, 278(16), 13928–13935.

    PubMed  CAS  Google Scholar 

  186. Brennan, S. E., Kuwano, Y., Alkharouf, N., Blackshear, P. J., Gorospe, M., & Wilson, G. M. (2009). The mRNA-destabilizing protein tristetraprolin is suppressed in many cancers, altering tumorigenic phenotypes and patient prognosis. Cancer Research, 69(12), 5168–5176.

    PubMed  CAS  Google Scholar 

  187. Sanduja, S., Kaza, V., & Dixon, D. A. (2009). The mRNA decay factor tristetraprolin (TTP) induces senescence in human papillomavirus-transformed cervical cancer cells by targeting E6-AP ubiquitin ligase. Aging, 1(9), 803–817.

    PubMed  CAS  Google Scholar 

  188. Blackshear, P. J., Lai, W. S., Kennington, E. A., Brewer, G., Wilson, G. M., Guan, X., et al. (2003). Characteristics of the interaction of a synthetic human tristetraprolin tandem zinc finger peptide with AU-rich element-containing RNA substrates. The Journal of Biological Chemistry, 278(22), 19947–19955.

    PubMed  CAS  Google Scholar 

  189. Brewer, B. Y., Malicka, J., Blackshear, P. J., & Wilson, G. M. (2004). RNA sequence elements required for high affinity binding by the zinc finger domain of tristetraprolin: conformational changes coupled to the bipartite nature of AU-rich mRNA-destabilizing motifs. The Journal of Biological Chemistry, 279(27), 27870–27877.

    PubMed  CAS  Google Scholar 

  190. Tian, Q., Streuli, M., Saito, H., Schlossman, S. F., & Anderson, P. (1991). A polyadenylate binding protein localized to the granules of cytolytic lymphocytes induces DNA fragmentation in target cells. Cell, 67(3), 629–639.

    PubMed  CAS  Google Scholar 

  191. Lopez de Silanes, I., Galban, S., Martindale, J. L., Yang, X., Mazan-Mamczarz, K., Indig, F. E., et al. (2005). Identification and functional outcome of mRNAs associated with RNA-binding protein TIA-1. Molecular and Cellular Biology, 25(21), 9520–9531.

    PubMed  CAS  Google Scholar 

  192. Dixon, D. A., Balch, G. C., Kedersha, N., Anderson, P., Zimmerman, G. A., Beauchamp, R. D., et al. (2003). Regulation of cyclooxygenase-2 expression by the translational silencer TIA-1. The Journal of Experimental Medicine, 198(3), 475–481.

    PubMed  CAS  Google Scholar 

  193. Phillips, K., Kedersha, N., Shen, L., Blackshear, P. J., & Anderson, P. (2004). Arthritis suppressor genes TIA-1 and TTP dampen the expression of tumor necrosis factor alpha, cyclooxygenase 2, and inflammatory arthritis. Proceedings of the National Academy of Sciences USA, 101(7), 2011–2016.

    CAS  Google Scholar 

  194. Menter, D. G., Schilsky, R. L., & DuBois, R. N. (2010). Cyclooxygenase-2 and cancer treatment: understanding the risk should be worth the reward. Clinical Cancer Research, 16(5), 1384–1390.

    PubMed  CAS  Google Scholar 

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Acknowledgments

The authors were funded by grants from the National Institutes of Health (R01CA134609) and American Cancer Society (RSG-06-122-01-CNE). We apologize to our colleagues for not being able to refer all primary work due to space limitations.

Author information

Authors and Affiliations

  1. Department of Biological Sciences and Center for Colon Cancer Research, University of South Carolina, Columbia, SC, USA

    Ashleigh E. Moore & Dan A. Dixon

  2. Novartis Institutes for Biomedical Research, RNAi Therapeutics, Cambridge, MA, USA

    Lisa E. Young

Authors
  1. Ashleigh E. Moore
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  2. Lisa E. Young
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  3. Dan A. Dixon
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Correspondence to Dan A. Dixon.

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Moore, A.E., Young, L.E. & Dixon, D.A. MicroRNA and AU-rich element regulation of prostaglandin synthesis. Cancer Metastasis Rev 30, 419–435 (2011). https://doi.org/10.1007/s10555-011-9300-5

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  • DOI: https://doi.org/10.1007/s10555-011-9300-5

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