Advertisement

Regulation of Autophagy by microRNAs: Implications in Cancer Therapy

Chapter
  • 555 Downloads
Part of the Current Cancer Research book series (CUCR)

Abstract

As an emerging hallmark of cancer, aberrant energy metabolism has drawn increasing attention in both basic research and clinical study. Autophagy is one of the main mechanisms for cells to maintain metabolic homeostasis, and cancer cells often display altered autophagic activity. Thus, autophagy is now pursued as a target for anti-cancer therapies. The current approaches to modulating autophagy include manipulation of either expressions or functions of the proteins that are key components of autophagic pathways. As a main post-transcriptional regulatory factor, microRNAs play important roles in various physiological and pathophysiological processes including cancers. Since miR-30a was first reported to regulate autophagy through targeting 3′ untranslated region (3′ UTR) of Beclin-1, a key autophagy regulatory gene, numerous miRNAs involved in autophagy regulation have been reported. Here we overview the current knowledge regarding the roles of miRNAs in regulation of autophagy and their implication in cancer therapy.

Keywords

Autophagy microRNA Post-transcriptional regulation Cancer therapy Cancer metabolism 

References

  1. Adlakha, Y. K., & Saini, N. (2011). MicroRNA-128 downregulates Bax and induces apoptosis in human embryonic kidney cells. Cellular and Molecular Life Sciences, 68(8), 1415–1428.PubMedCrossRefGoogle Scholar
  2. Aliabadi, H. M., Landry, B., Sun, C., Tang, T., & Uludag, H. (2012). Supramolecular assemblies in functional siRNA delivery: Where do we stand? Biomaterials, 33(8), 2546–2569.PubMedCrossRefGoogle Scholar
  3. Amaravadi, R. K., et al. (2007). Autophagy inhibition enhances therapy-induced apoptosis in a Myc-induced model of lymphoma. Journal of Clinical Investigation, 117(2), 326–336.PubMedPubMedCentralCrossRefGoogle Scholar
  4. Ameres, S. L., & Zamore, P. D. (2013). Diversifying microRNA sequence and function. Nature Reviews Molecular Cell Biology, 14(8), 475–488.PubMedCrossRefGoogle Scholar
  5. Aravin, A., & Tuschl, T. (2005). Identification and characterization of small RNAs involved in RNA silencing. FEBS Letters, 579(26), 5830–5840.PubMedCrossRefGoogle Scholar
  6. Artavanis-Tsakonas, S., Rand, M. D., & Lake, R. J. (1999). Notch signaling: Cell fate control and signal integration in development. Science, 284(5415), 770–776.PubMedCrossRefGoogle Scholar
  7. Bader, A. G., Brown, D., Stoudemire, J., & Lammers, P. (2011). Developing therapeutic microRNAs for cancer. Gene Therapy, 18(12), 1121–1126.PubMedPubMedCentralCrossRefGoogle Scholar
  8. Bernstein, E., Caudy, A. A., Hammond, S. M., & Hannon, G. J. (2001). Role for a bidentate ribonuclease in the initiation step of RNA interference. Nature, 409(6818), 363–366.PubMedCrossRefGoogle Scholar
  9. Berry, D. L., & Baehrecke, E. H. (2008). Autophagy functions in programmed cell death. Autophagy, 4(3), 359–360.PubMedPubMedCentralCrossRefGoogle Scholar
  10. Bo, L., Su-Ling, D., Fang, L., Lu-Yu, Z., Tao, A., Stefan, D., et al. (2014). Autophagic program is regulated by miR-325. Cell Death and Differentiation, 21(6), 967–977.PubMedPubMedCentralCrossRefGoogle Scholar
  11. Bouchie, A. (2013). First microRNA mimic enters clinic. Nature Biotechnology, 31(7), 577.PubMedCrossRefGoogle Scholar
  12. Braconi, C., Valeri, N., Gasparini, P., Huang, N., Taccioli, C., & Nuovo, G. (2010). Hepatitis C virus proteins modulate microRNA expression and chemosensitivity in malignant hepatocytes. Clinical Cancer Research, 16(3), 957–966.PubMedPubMedCentralCrossRefGoogle Scholar
  13. Brest, P., Lapaquette, P., Souidi, M., Lebrigand, K., Cesaro, A., & Vouret-Craviari, V. (2011). A synonymous variant in IRGM alters a binding site for miR-196 and causes deregulation of IRGM-dependent xenophagy in Crohn’s disease. Nature Genetics, 43(3), 242–245.PubMedCrossRefGoogle Scholar
  14. Chang, Y., Lin, J., & Tsung, A. (2012a). Manipulation of autophagy by MIR375 generates antitumor effects in liver cancer. Autophagy, 8(12), 1833–1834.PubMedPubMedCentralCrossRefGoogle Scholar
  15. Chang, Y., Yan, W., He, X., Zhang, L., Li, C., & Huang, H. (2012b). miR-375 inhibits autophagy and reduces viability of hepatocellular carcinoma cells under hypoxic conditions. Gastroenterology, 143(1), 177–187 e8.PubMedCrossRefGoogle Scholar
  16. Chatterjee, A., Chattopadhyay, D., Chakrabarti, G. (2014). miR-17-5p downregulation contributes to paclitaxel resistance of lung cancer cells through altering beclin1 expression. PLoS One, 9(4), e95716.Google Scholar
  17. Chen, Y., Fu, L. L., Wen, X., Liu, B., Huang, J., & Wang, J. H. (2014). Oncogenic and tumor suppressive roles of microRNAs in apoptosis and autophagy. Apoptosis, 19(8), 1177–1189.PubMedCrossRefGoogle Scholar
  18. Christoffersen, N. R., Shalgi, R., Frankel, L. B., Leucci, E., Lees, M., & Klausen, M. (2010). p53-independent upregulation of miR-34a during oncogene-induced senescence represses MYC. Cell Death and Differentiation, 17(2), 236–245.PubMedCrossRefGoogle Scholar
  19. Cimino, D., De Pitta, C., Orso, F., Zampini, M., Casara, S., & Penna, E. (2013). miR148b is a major coordinator of breast cancer progression in a relapse-associated microRNA signature by targeting ITGA5, ROCK1, PIK3CA, NRAS, and CSF1. FASEB Journal, 27(3), 1223–1235.PubMedCrossRefGoogle Scholar
  20. Ciuffreda, L., Di Sanza, C., Incani, U. C., & Milella, M. (2010). The mTOR pathway: A new target in cancer therapy. Current Cancer Drug Targets, 10(5), 484–495.PubMedCrossRefGoogle Scholar
  21. Claerhout, S., Verschooten, L., Van Kelst, S., De Vos, R., Proby, C., & Agostinis, P. (2010). Concomitant inhibition of AKT and autophagy is required for efficient cisplatin-induced apoptosis of metastatic skin carcinoma. International Journal of Cancer, 127(12), 2790–2803.PubMedCrossRefGoogle Scholar
  22. Clark, J. W., & Longo, D. L. (2015). Cancer cell biology. In D. Kasper et al. (Eds.), Harrison’s principles of internal medicine, 19e. New York, NY: McGraw-Hill Education.Google Scholar
  23. Clarke, P. G., & Puyal, J. (2012). Autophagic cell death exists. Autophagy, 8(6), 867–869.PubMedPubMedCentralCrossRefGoogle Scholar
  24. Comincini, S., Allavena, G., Palumbo, S., Morini, M., Durando, F., & Angeletti, F. (2013). microRNA-17 regulates the expression of ATG7 and modulates the autophagy process, improving the sensitivity to temozolomide and low-dose ionizing radiation treatments in human glioblastoma cells. Cancer Biology and Therapy, 14(7), 574–586.PubMedPubMedCentralCrossRefGoogle Scholar
  25. Cougot, N., Babajko, S., & Seraphin, B. (2004). Cytoplasmic foci are sites of mRNA decay in human cells. Journal of Cell Biology, 165(1), 31–40.PubMedPubMedCentralCrossRefGoogle Scholar
  26. Dai, X., & Tan, C. (2015). Combination of microRNA therapeutics with small-molecule anticancer drugs: Mechanism of action and co-delivery nanocarriers. Advanced Drug Delivery Reviews, 81, 184–197.PubMedCrossRefGoogle Scholar
  27. Dai, F., Zhang, Y., & Chen, Y. (2014). Involvement of miR-29b signaling in the sensitivity to chemotherapy in patients with ovarian carcinoma. Human Pathology, 45(6), 1285–1293.PubMedCrossRefGoogle Scholar
  28. Daka, A., & Peer, D. (2012). RNAi-based nanomedicines for targeted personalized therapy. Advanced Drug Delivery Reviews, 64(13), 1508–1521.PubMedCrossRefGoogle Scholar
  29. Denton, D., Shravage, B., Simin, R., Mills, K., Berry, D. L., & Baehrecke, E. H. (2009). Autophagy, not apoptosis, is essential for midgut cell death in Drosophila. Current Biology, 19(20), 1741–1746.PubMedPubMedCentralCrossRefGoogle Scholar
  30. Denton, D., Xu, T., & Kumar, S. (2015). Autophagy as a pro-death pathway. Immunology and Cell Biology, 93(1), 35–42.PubMedCrossRefGoogle Scholar
  31. Deter, R. L., & De Duve, C. (1967). Influence of glucagon, an inducer of cellular autophagy, on some physical properties of rat liver lysosomes. Journal of Cell Biology, 33(2), 437–449.PubMedPubMedCentralCrossRefGoogle Scholar
  32. Ding, X. Q., Ge, P. C., Liu, Z., Jia, H., Chen, X., & An, F. H. (2015). Interaction between microRNA expression and classical risk factors in the risk of coronary heart disease. Scientific Reports, 5, 14925.PubMedPubMedCentralCrossRefGoogle Scholar
  33. Donadelli, M., & Palmieri, M. (2013). Roles for microRNA 23b in regulating autophagy and development of pancreatic adenocarcinoma. Gastroenterology, 145(5), 936–938.PubMedCrossRefGoogle Scholar
  34. Du, T., & Zamore, P. D. (2005). microPrimer: The biogenesis and function of microRNA. Development, 132(21), 4645–4652.PubMedCrossRefGoogle Scholar
  35. Evdokimova, V., Ruzanov, P., Imataka, H., Raught, B., Svitkin, Y., & Ovchinnikov, L. P. (2001). The major mRNA-associated protein YB-1 is a potent 5′ cap-dependent mRNA stabilizer. EMBO Journal, 20(19), 5491–5502.PubMedPubMedCentralCrossRefGoogle Scholar
  36. Feng, Y., He, D., Yao, Z., & Klionsky, D. J. (2014). The machinery of macroautophagy. Cell Research, 24(1), 24–41.PubMedCrossRefGoogle Scholar
  37. Fornari, F., Milazzo, M., Chieco, P., Negrini, M., Calin, G. A., & Grazi, G. L. (2010). MiR-199a-3p regulates mTOR and c-Met to influence the doxorubicin sensitivity of human hepatocarcinoma cells. Cancer Research, 70(12), 5184–5193.PubMedCrossRefGoogle Scholar
  38. Frankel, L. B., & Lund, A. H. (2012). MicroRNA regulation of autophagy. Carcinogenesis, 33(11), 2018–2025.PubMedCrossRefGoogle Scholar
  39. Frankel, L. B., Wen, J., Lees, M., Hoyer-Hansen, M., Farkas, T., & Krogh, A. (2011). microRNA-101 is a potent inhibitor of autophagy. EMBO Journal, 30(22), 4628–4641.PubMedPubMedCentralCrossRefGoogle Scholar
  40. Fujiya, M., Konishi, H., Mohamed Kamel, M. K., Ueno, N., Inaba, Y., & Moriichi, K. (2014). microRNA-18a induces apoptosis in colon cancer cells via the autophagolysosomal degradation of oncogenic heterogeneous nuclear ribonucleoprotein A1. Oncogene, 33(40), 4847–4856.PubMedCrossRefGoogle Scholar
  41. Gao, M., Fritz, D. T., Ford, L. P., & Wilusz, J. (2000). Interaction between a poly(A)-specific ribonuclease and the 5’ cap influences mRNA deadenylation rates in vitro. Molecular Cell, 5(3), 479–488.Google Scholar
  42. Gibbings, D., Mostowy, S., Jay, F., Schwab, Y., Cossart, P., & Voinnet, O. (2012). Selective autophagy degrades DICER and AGO2 and regulates miRNA activity. Nature Cell Biology, 14(12), 1314–1321.PubMedPubMedCentralCrossRefGoogle Scholar
  43. Gibbings, D., Mostowy, S., & Voinnet, O. (2013). Autophagy selectively regulates miRNA homeostasis. Autophagy, 9(5), 781–783.PubMedPubMedCentralCrossRefGoogle Scholar
  44. Glick, D., Barth, S., & Macleod, K. F. (2010). Autophagy: Cellular and molecular mechanisms. Journal of Pathology, 221(1), 3–12.PubMedPubMedCentralCrossRefGoogle Scholar
  45. Gordy, C., & He, Y. W. (2012). The crosstalk between autophagy and apoptosis: Where does this lead? Protein & Cell, 3(1), 17–27.CrossRefGoogle Scholar
  46. Gottlieb, R. A. (2010). Apoptosis. In M. A. Lichtman et al. (Eds.), Williams hematology. New York, NY: McGraw-Hill.Google Scholar
  47. Guo, J. Y., Xia, B., & White, E. (2013). Autophagy-mediated tumor promotion. Cell, 155(6), 1216–1219.PubMedPubMedCentralCrossRefGoogle Scholar
  48. Gupta, S., Verma, S., Mantri, S., Berman, N. E., & Sandhir, R. (2015). Targeting MicroRNAs in Prevention and Treatment of Neurodegenerative Disorders. Drug Development and Research, 76(7), 397–418.CrossRefGoogle Scholar
  49. Gwak, H. S., Kim, T. H., Jo, G. H., Kim, Y. J., Kwak, H. J., & Kim, J. H. (2012). Silencing of microRNA-21 confers radio-sensitivity through inhibition of the PI3K/AKT pathway and enhancing autophagy in malignant glioma cell lines. PLoS One, 7(10), e47449.PubMedPubMedCentralCrossRefGoogle Scholar
  50. Hailey, D. W., Rambold, A. S., Satpute-Krishnan, P., Mitra, K., Sougrat, R., & Kim, P. K. (2010). Mitochondria supply membranes for autophagosome biogenesis during starvation. Cell, 141(4), 656–667.PubMedPubMedCentralCrossRefGoogle Scholar
  51. Hall, D. P., Cost, N. G., Hegde, S., Kellner, E., Mikhaylova, O., & Stratton, Y. (2014). TRPM3 and miR-204 establish a regulatory circuit that controls oncogenic autophagy in clear cell renal cell carcinoma. Cancer Cell, 26(5), 738–753.PubMedPubMedCentralCrossRefGoogle Scholar
  52. Harhaji-Trajkovic, L., Vilimanovich, U., Kravic-Stevovic, T., Bumbasirevic, V., & Trajkovic, V. (2009). AMPK-mediated autophagy inhibits apoptosis in cisplatin-treated tumour cells. J Cell Mol Med, 13(9b), 3644–3654.PubMedCrossRefGoogle Scholar
  53. Hock, J., & Meister, G. (2008). The Argonaute protein family. Genome Biology, 9(2), 210.PubMedPubMedCentralCrossRefGoogle Scholar
  54. Huang, Y., Shen, X. J., Zou, Q., Wang, S. P., Tang, S. M., & Zhang, G. Z. (2011a). Biological functions of microRNAs: a review. Journal of Physiology and Biochemistry, 67(1), 129–139.PubMedCrossRefGoogle Scholar
  55. Huang, Y., Chuang, A. Y., & Ratovitski, E. A. (2011b). Phospho-DeltaNp63alpha/miR-885-3p axis in tumor cell life and cell death upon cisplatin exposure. Cell Cycle, 10(22), 3938–3947.PubMedPubMedCentralCrossRefGoogle Scholar
  56. Huang, Y., Guerrero-Preston, R., & Ratovitski, E. A. (2012). Phospho-DeltaNp63alpha-dependent regulation of autophagic signaling through transcription and micro-RNA modulation. Cell Cycle, 11(6), 1247–1259.PubMedPubMedCentralCrossRefGoogle Scholar
  57. Ichimura, Y., Kirisako, T., Takao, T., Satomi, Y., Shimonishi, Y., & Ishihara, N. (2000). A ubiquitin-like system mediates protein lipidation. Nature, 408(6811), 488–492.PubMedCrossRefGoogle Scholar
  58. Itakura, E., Kishi-Itakura, C., & Mizushima, N. (2012). The hairpin-type tail-anchored SNARE syntaxin 17 targets to autophagosomes for fusion with endosomes/lysosomes. Cell, 151(6), 1256–1269.PubMedCrossRefGoogle Scholar
  59. Iwakawa, H. O., & Tomari, Y. (2015). The functions of MicroRNAs: mRNA decay and translational repression. Trends in Cell Biology, 25(11), 651–665.PubMedCrossRefGoogle Scholar
  60. Iyer, D., Chang, D., Marx, J., Wei, L., Olson, E. N., & Parmacek, M. S. (2006). Serum response factor MADS box serine-162 phosphorylation switches proliferation and myogenic gene programs. Proceedings of the National Academy of Sciences of the United States of America, 103(12), 4516–4521.PubMedPubMedCentralCrossRefGoogle Scholar
  61. Janssen, H. L., Reesink, H. W., Lawitz, E. J., Zeuzem, S., Rodriguez-Torres, M., & Patel, K. (2013). Treatment of HCV infection by targeting microRNA. New England Journal of Medicine, 368(18), 1685–1694.PubMedCrossRefGoogle Scholar
  62. Jiang, P., & Mizushima, N. (2014). Autophagy and human diseases. Cell Research, 24(1), 69–79.PubMedCrossRefGoogle Scholar
  63. Jing, Q., Huang, S., Guth, S., Zarubin, T., Motoyama, A., & Chen, J. (2005). Involvement of microRNA in AU-rich element-mediated mRNA instability. Cell, 120(5), 623–634.PubMedCrossRefGoogle Scholar
  64. Jing, Z., Han, W., Sui, X., Xie, J., & Pan, H. (2015). Interaction of autophagy with microRNAs and their potential therapeutic implications in human cancers. Cancer Letters, 356(2 Pt B), 332–338.PubMedCrossRefGoogle Scholar
  65. Johnston, R. J., & Hobert, O. (2003). A microRNA controlling left/right neuronal asymmetry in Caenorhabditis elegans. Nature, 426(6968), 845–849.PubMedCrossRefGoogle Scholar
  66. Johnston, R. J., Jr., Chang, S., Etchberger, J. F., Ortiz, C. O., & Hobert, O. (2005). MicroRNAs acting in a double-negative feedback loop to control a neuronal cell fate decision. Proceedings of the National Academy of Sciences of the United States of America, 102(35), 12449–12454.PubMedPubMedCentralCrossRefGoogle Scholar
  67. Kaminskyy, V., & Zhivotovsky, B. (2012). Proteases in autophagy. Biochimica et Biophysica Acta, 1824(1), 44–50.PubMedCrossRefGoogle Scholar
  68. Kang, R., Zeh, H. J., Lotze, M. T., & Tang, D. (2011). The Beclin 1 network regulates autophagy and apoptosis. Cell Death and Differentiation, 18(4), 571–580.PubMedPubMedCentralCrossRefGoogle Scholar
  69. Kim, V. N. (2006). Small RNAs just got bigger: Piwi-interacting RNAs (piRNAs) in mammalian testes. Genes and Development, 20(15), 1993–1997.PubMedCrossRefGoogle Scholar
  70. Klionsky, D. J. (2007). Autophagy: From phenomenology to molecular understanding in less than a decade. Nature Reviews Molecular Cell Biology, 8(11), 931–937.PubMedCrossRefGoogle Scholar
  71. Korkmaz, G., le Sage, C., Tekirdag, K. A., Agami, R., & Gozuacik, D. (2012). miR-376b controls starvation and mTOR inhibition-related autophagy by targeting ATG4C and BECN1. Autophagy, 8(2), 165–176.PubMedCrossRefGoogle Scholar
  72. Kroemer, G., Marino, G., & Levine, B. (2010). Autophagy and the integrated stress response. Molecular Cell, 40(2), 280–293.PubMedPubMedCentralCrossRefGoogle Scholar
  73. Krol, J., Loedige, I., & Filipowicz, W. (2010). The widespread regulation of microRNA biogenesis, function and decay. Nature Reviews Genetics, 11(9), 597–610.PubMedGoogle Scholar
  74. Lai, E. C. (2002). Micro RNAs are complementary to 3′ UTR sequence motifs that mediate negative post-transcriptional regulation. Nature Genetics, 30(4), 363–364.PubMedCrossRefGoogle Scholar
  75. Lan, S. H., Wu, S. Y., Zuchini, R., Lin, X. Z., Su, I. J., & Tsai, T. F. (2014a). Autophagy-preferential degradation of MIR224 participates in hepatocellular carcinoma tumorigenesis. Autophagy, 10(9), 1687–1689.PubMedPubMedCentralCrossRefGoogle Scholar
  76. Lan, S. H., Wu, S. Y., Zuchini, R., Lin, X. Z., Su, I. J., & Tsai, T. F. (2014b). Autophagy suppresses tumorigenesis of hepatitis B virus-associated hepatocellular carcinoma through degradation of microRNA-224. Hepatology, 59(2), 505–517.PubMedCrossRefGoogle Scholar
  77. Lavandero, S., Troncoso, R., Rothermel, B. A., Martinet, W., Sadoshima, J., & Hill, J. A. (2013). Cardiovascular autophagy: concepts, controversies, and perspectives. Autophagy, 9(10), 1455–1466.PubMedCrossRefGoogle Scholar
  78. Lee, Y., Ahn, C., Han, J., Choi, H., Kim, J., & Yim, J. (2003). The nuclear RNase III Drosha initiates microRNA processing. Nature, 425(6956), 415–419.PubMedCrossRefGoogle Scholar
  79. Leung, A. K. (2015). The whereabouts of microRNA actions: Cytoplasm and beyond. Trends in Cell Biology, 25(10), 601–610.PubMedPubMedCentralCrossRefGoogle Scholar
  80. Leung, A. K., Calabrese, J. M., & Sharp, P. A. (2006). Quantitative analysis of Argonaute protein reveals microRNA-dependent localization to stress granules. Proceedings of the National Academy of Sciences of the United States of America, 103(48), 18125–18130.PubMedPubMedCentralCrossRefGoogle Scholar
  81. Leung, A. K., Vyas, S., Rood, J. E., Bhutkar, A., Sharp, P. A., & Chang, P. (2011). Poly(ADP-ribose) regulates stress responses and microRNA activity in the cytoplasm. Molecular Cell, 42(4), 489–499.PubMedPubMedCentralCrossRefGoogle Scholar
  82. Levine, B., & Klionsky, D. J. (2004). Development by self-digestion: Molecular mechanisms and biological functions of autophagy. Developmental Cell, 6(4), 463–477.PubMedCrossRefGoogle Scholar
  83. Levine, B., & Kroemer, G. (2008). Autophagy in the pathogenesis of disease. Cell, 132(1), 27–42.PubMedPubMedCentralCrossRefGoogle Scholar
  84. Levine, B., & Kroemer, G. (2009). Autophagy in aging, disease and death: The true identity of a cell death impostor. Cell Death and Differentiation, 16(1), 1–2.PubMedPubMedCentralCrossRefGoogle Scholar
  85. Lewis, B. P., Burge, C. B., & Bartel, D. P. (2005). Conserved seed pairing, often flanked by adenosines, indicates that thousands of human genes are microRNA targets. Cell, 120(1), 15–20.PubMedCrossRefGoogle Scholar
  86. Lewis, J. D., & Izaurralde, E. (1997). The role of the cap structure in RNA processing and nuclear export. European Journal of Biochemistry, 247(2), 461–469.PubMedCrossRefGoogle Scholar
  87. Li, F., & Vierstra, R. D. (2012). Autophagy: A multifaceted intracellular system for bulk and selective recycling. Trends in Plant Science, 17(9), 526–537.PubMedCrossRefGoogle Scholar
  88. Li, X., Xu, H. L., Liu, Y. X., An, N., Zhao, S., & Bao, J. K. (2013). Autophagy modulation as a target for anticancer drug discovery. Acta Pharmacologica Sinica, 34(5), 612–624.PubMedPubMedCentralCrossRefGoogle Scholar
  89. Liang, X. H., Jackson, S., Seaman, M., Brown, K., Kempkes, B., & Hibshoosh, H. (1999). Induction of autophagy and inhibition of tumorigenesis by beclin 1. Nature, 402(6762), 672–676.PubMedCrossRefGoogle Scholar
  90. Liao, W. T., Ye, Y. P., Zhang, N. J., Li, T. T., Wang, S. Y., & Cui, Y. M. (2014). MicroRNA-30b functions as a tumour suppressor in human colorectal cancer by targeting KRAS, PIK3CD and BCL2. Journal of Pathology, 232(4), 415–427.PubMedCrossRefGoogle Scholar
  91. Liu, J., Valencia-Sanchez, M. A., Hannon, G. J., & Parker, R. (2005). MicroRNA-dependent localization of targeted mRNAs to mammalian P-bodies. Nature Cell Biology, 7(7), 719–723.PubMedPubMedCentralCrossRefGoogle Scholar
  92. Liu, Y. N., Yang, X., Suo, Z. W., Xu, Y. M., & Hu, X. D. (2014). Fyn kinase-regulated NMDA receptor- and AMPA receptor-dependent pain sensitization in spinal dorsal horn of mice. European Journal of Pain, 18(8), 1120–1128.PubMedCrossRefGoogle Scholar
  93. Longatti, A., Lamb, C. A., Razi, M., Yoshimura, S., Barr, F. A., & Tooze, S. A. (2012). TBC1D14 regulates autophagosome formation via Rab11- and ULK1-positive recycling endosomes. Journal of Cell Biology, 197(5), 659–675.PubMedPubMedCentralCrossRefGoogle Scholar
  94. Maiuri, M. C., Zalckvar, E., Kimchi, A., & Kroemer, G. (2007). Self-eating and self-killing: crosstalk between autophagy and apoptosis. Nature Reviews Molecular Cell Biology, 8(9), 741–752.PubMedCrossRefGoogle Scholar
  95. Majid, S., Dar, A. A., Saini, S., Deng, G., Chang, I., & Greene, K. (2013). MicroRNA-23b functions as a tumor suppressor by regulating Zeb1 in bladder cancer. PLoS One, 8(7), e67686.PubMedPubMedCentralCrossRefGoogle Scholar
  96. Menghini, R., Casagrande, V., Marino, A., Marchetti, V., Cardellini, M., & Stoehr, R. (2014). MiR-216a: a link between endothelial dysfunction and autophagy. Cell Death Dis, 5, e1029.PubMedPubMedCentralCrossRefGoogle Scholar
  97. Mikhaylova, O., Stratton, Y., Hall, D., Kellner, E., Ehmer, B., & Drew, A. F. (2012). VHL-regulated MiR-204 suppresses tumor growth through inhibition of LC3B-mediated autophagy in renal clear cell carcinoma. Cancer Cell, 21(4), 532–546.PubMedPubMedCentralCrossRefGoogle Scholar
  98. Miller, T. E., Ghoshal, K., Ramaswamy, B., Roy, S., Datta, J., & Shapiro, C. L. (2008). MicroRNA-221/222 confers tamoxifen resistance in breast cancer by targeting p27Kip1. Journal of Biological Chemistry, 283(44), 29897–29903.PubMedPubMedCentralCrossRefGoogle Scholar
  99. Mizushima, N. (2007). Autophagy: Process and function. Genes and Development, 21(22), 2861–2873.PubMedCrossRefGoogle Scholar
  100. Mizushima, N., & Komatsu, M. (2011). Autophagy: Renovation of cells and tissues. Cell, 147(4), 728–741.PubMedCrossRefGoogle Scholar
  101. Mizushima, N., Noda, T., & Ohsumi, Y. (1999). Apg16p is required for the function of the Apg12p-Apg5p conjugate in the yeast autophagy pathway. EMBO Journal, 18(14), 3888–3896.PubMedPubMedCentralCrossRefGoogle Scholar
  102. Mizushima, N., Levine, B., Cuervo, A. M., & Klionsky, D. J. (2008). Autophagy fights disease through cellular self-digestion. Nature, 451(7182), 1069–1075.PubMedPubMedCentralCrossRefGoogle Scholar
  103. Nakatogawa, H., Suzuki, K., Kamada, Y., & Ohsumi, Y. (2009). Dynamics and diversity in autophagy mechanisms: lessons from yeast. Nature Reviews Molecular Cell Biology, 10(7), 458–467.PubMedCrossRefGoogle Scholar
  104. Oneyama, C., Ikeda, J., Okuzaki, D., Suzuki, K., Kanou, T., & Shintani, Y. (2011). MicroRNA-mediated downregulation of mTOR/FGFR3 controls tumor growth induced by Src-related oncogenic pathways. Oncogene, 30(32), 3489–3501.PubMedCrossRefGoogle Scholar
  105. Pan, B., Yi, J., & Song, H. (2013). MicroRNA-mediated autophagic signaling networks and cancer chemoresistance. Cancer Biotherapy and Radiopharmaceuticals, 28(8), 573–578.PubMedPubMedCentralCrossRefGoogle Scholar
  106. Pasquinelli, A. E., Reinhart, B. J., Slack, F., Martindale, M. Q., Kuroda, M. I., & Maller, B. (2000). Conservation of the sequence and temporal expression of let-7 heterochronic regulatory RNA. Nature, 408(6808), 86–89.PubMedCrossRefGoogle Scholar
  107. Pavlides, S., Tsirigos, A., Migneco, G., Whitaker-Menezes, D., Chiavarina, B., & Flomenberg, N. (2010). The autophagic tumor stroma model of cancer: Role of oxidative stress and ketone production in fueling tumor cell metabolism. Cell Cycle, 9(17), 3485–3505.PubMedPubMedCentralCrossRefGoogle Scholar
  108. Peng, X., Li, W., Yuan, L., Mehta, R. G., Kopelovich, L., & McCormick, D. L. (2013). Inhibition of proliferation and induction of autophagy by atorvastatin in PC3 prostate cancer cells correlate with downregulation of Bcl2 and upregulation of miR-182 and p21. PLoS One, 8(8), e70442.PubMedPubMedCentralCrossRefGoogle Scholar
  109. Pennati, M., Lopergolo, A., Profumo, V., De Cesare, M., Sbarra, S., & Valdagni, R. (2014). miR-205 impairs the autophagic flux and enhances cisplatin cytotoxicity in castration-resistant prostate cancer cells. Biochemical Pharmacology, 87(4), 579–597.PubMedCrossRefGoogle Scholar
  110. Puri, C., Renna, M., Bento, C. F., Moreau, K., & Rubinsztein, D. C. (2013). Diverse autophagosome membrane sources coalesce in recycling endosomes. Cell, 154(6), 1285–1299.PubMedPubMedCentralCrossRefGoogle Scholar
  111. Qased, A. B., Yi, H., Liang, N., Ma, S., Qiao, S., & Liu, X. (2013). MicroRNA-18a upregulates autophagy and ataxia telangiectasia mutated gene expression in HCT116 colon cancer cells. Molecular Medicine Reports, 7(2), 559–564.PubMedGoogle Scholar
  112. Radogna, F., Dicato, M., & Diederich, M. (2015). Cancer-type-specific crosstalk between autophagy, necroptosis and apoptosis as a pharmacological target. Biochemical Pharmacology, 94(1), 1–11.PubMedCrossRefGoogle Scholar
  113. Ramalinga, M., Roy, A., Srivastava, A., Bhattarai, A., Harish, V., & Suy, S. (2015). MicroRNA-212 negatively regulates starvation induced autophagy in prostate cancer cells by inhibiting SIRT1 and is a modulator of angiogenesis and cellular senescence. Oncotarget, 6(33), 34446–34457.PubMedPubMedCentralGoogle Scholar
  114. Rao, S., Tortola, L., Perlot, T., Wirnsberger, G., Novatchkova, M., & Nitsch, R. (2014). A dual role for autophagy in a murine model of lung cancer. Nature Communications, 5, 3056.Google Scholar
  115. Ravikumar, B., Moreau, K., Jahreiss, L., Puri, C., & Rubinsztein, D. C. (2010). Plasma membrane contributes to the formation of pre-autophagosomal structures. Nature Cell Biology, 12(8), 747–757.PubMedPubMedCentralCrossRefGoogle Scholar
  116. Reinhart, B. J., Slack, F. J., Basson, M., Pasquinelli, A. E., Bettinger, J. C., & Rougvie, A. E. (2000). The 21-nucleotide let-7 RNA regulates developmental timing in Caenorhabditis elegans. Nature, 403(6772), 901–906.PubMedCrossRefGoogle Scholar
  117. Ren, J. H., He, W. S., Nong, L., Zhu, Q. Y., Hu, K., & Zhang, R. G. (2010). Acquired cisplatin resistance in human lung adenocarcinoma cells is associated with enhanced autophagy. Cancer Biotherapy and Radiopharmaceuticals, 25(1), 75–80.PubMedCrossRefGoogle Scholar
  118. Russell, R. C., Yuan, H. X., & Guan, K. L. (2014). Autophagy regulation by nutrient signaling. Cell Research, 24(1), 42–57.PubMedCrossRefGoogle Scholar
  119. Schroeder, A., Heller, D. A., Winslow, M. M., Dahlman, J. E., Pratt, G. W., & Langer, R. (2012). Treating metastatic cancer with nanotechnology. Nature Reviews Cancer, 12(1), 39–50.CrossRefGoogle Scholar
  120. Schweichel, J. U., & Merker, H. J. (1973). The morphology of various types of cell death in prenatal tissues. Teratology, 7(3), 253–266.PubMedCrossRefGoogle Scholar
  121. Sen, G. L., & Blau, H. M. (2005). Argonaute 2/RISC resides in sites of mammalian mRNA decay known as cytoplasmic bodies. Nature Cell Biology, 7(6), 633–636.PubMedCrossRefGoogle Scholar
  122. Seoudi, A. M., Lashine, Y. A., & Abdelaziz, A. I. (2012). MicroRNA-181a—A tale of discrepancies. Expert Reviews in Molecular Medicine, 14, e5.PubMedCrossRefGoogle Scholar
  123. Shahbazi, J., Lock, R., & Liu, T. (2013). Tumor protein 53-induced nuclear protein 1 enhances p53 function and represses tumorigenesis. Frontiers in Genetics, 4, 80.PubMedPubMedCentralCrossRefGoogle Scholar
  124. Shi, Y., Chen, C., Zhang, X., Liu, Q., Xu, J. L., & Zhang, H. R. (2014). Primate-specific miR-663 functions as a tumor suppressor by targeting PIK3CD and predicts the prognosis of human glioblastoma. Clinical Cancer Research, 20(7), 1803–1813.PubMedCrossRefGoogle Scholar
  125. Shintani, T., & Klionsky, D. J. (2004). Autophagy in health and disease: A double-edged sword. Science, 306(5698), 6.CrossRefGoogle Scholar
  126. Singh, S. B., Ornatowski, W., Vergne, I., Naylor, J., Delgado, M., & Roberts, E. (2010). Human IRGM regulates autophagy and cell-autonomous immunity functions through mitochondria. Nature Cell Biology, 12(12), 1154–1165.PubMedPubMedCentralCrossRefGoogle Scholar
  127. Sonenberg, N., & Gingras, A. C. (1998). The mRNA 5′ cap-binding protein eIF4E and control of cell growth. Current Opinion in Cell Biology, 10(2), 268–275.PubMedCrossRefGoogle Scholar
  128. Stark, A., Brennecke, J., Russell, R. B., & Cohen, S. M. (2003). Identification of Drosophila MicroRNA targets. PLoS Biology, 1(3), E60.PubMedPubMedCentralCrossRefGoogle Scholar
  129. Stiuso, P., Potenza, N., Lombardi, A., Ferrandino, I., Monaco, A., & Zappavigna, S. (2015). MicroRNA-423-5p Promotes Autophagy in Cancer Cells and Is Increased in Serum From Hepatocarcinoma Patients Treated With Sorafenib. Molecular Therapy Nucleic Acids, 4, e233.PubMedCrossRefGoogle Scholar
  130. Su, Z., Yang, Z., Xu, Y., Chen, Y., & Yu, Q. (2015). MicroRNAs in apoptosis, autophagy and necroptosis. Oncotarget, 6(11), 8474–8490.PubMedPubMedCentralCrossRefGoogle Scholar
  131. Sui, X., Jin, L., Huang, X., Geng, S., He, C., & Hu, X. (2011). p53 signaling and autophagy in cancer: a revolutionary strategy could be developed for cancer treatment. Autophagy, 7(6), 565–571.PubMedCrossRefGoogle Scholar
  132. Sui, X., Zhu, J., Zhou, J., Wang, X., Li, D., & Han, W. (2015). Epigenetic modifications as regulatory elements of autophagy in cancer. Cancer Letters, 360(2), 106–113.PubMedCrossRefGoogle Scholar
  133. Sumbul, A. T., Gogebakan, B., Ergun, S., Yengil, E., Batmaci, C. Y., & Tonyali, O. (2014). miR-204-5p expression in colorectal cancer: an autophagy-associated gene. Tumour Biology, 35(12), 12713–12719.PubMedCrossRefGoogle Scholar
  134. Sun, Q., Liu, T., Yuan, Y., Guo, Z., Xie, G., & Du, S. (2015). MiR-200c inhibits autophagy and enhances radiosensitivity in breast cancer cells by targeting UBQLN1. International Journal of Cancer, 136(5), 1003–1012.PubMedCrossRefGoogle Scholar
  135. Tazawa, H., Yano, S., Yoshida, R., Yamasaki, Y., Sasaki, T., & Hashimoto, Y. (2012). Genetically engineered oncolytic adenovirus induces autophagic cell death through an E2F1-microRNA-7-epidermal growth factor receptor axis. International Journal of Cancer, 131(12), 2939–2950.PubMedCrossRefGoogle Scholar
  136. van Solinge, W. W., & van Wijk, R. (2015). Erythrocyte enzyme disorders. In K. Kaushansky et al. (Eds.), Williams hematology. New York, NY: McGraw-Hill Education.Google Scholar
  137. Visa, N., Izaurralde, E., Ferreira, J., Daneholt, B., & Mattaj, I. W. (1996). A nuclear cap-binding complex binds Balbiani ring pre-mRNA cotranscriptionally and accompanies the ribonucleoprotein particle during nuclear export. Journal of Cell Biology, 133(1), 5–14.PubMedCrossRefGoogle Scholar
  138. Wan, G., Xie, W., Liu, Z., Xu, W., Lao, Y., & Huang, N. (2014). Hypoxia-induced MIR155 is a potent autophagy inducer by targeting multiple players in the MTOR pathway. Autophagy, 10(1), 70–79.PubMedPubMedCentralCrossRefGoogle Scholar
  139. Wang, C. W., & Klionsky, D. J. (2003). The molecular mechanism of autophagy. Molecular Medicine, 9(3–4), 65–76.PubMedPubMedCentralGoogle Scholar
  140. Wang, J., Yang, K., Zhou, L., Minhaowu, Wu, Y., & Zhu, M. (2013a). MicroRNA-155 promotes autophagy to eliminate intracellular mycobacteria by targeting Rheb. PLoS Pathogens, 9(10), e1003697.Google Scholar
  141. Wang, P., Zhang, J., Zhang, L., Zhu, Z., Fan, J., & Chen, L. (2013b). MicroRNA 23b regulates autophagy associated with radioresistance of pancreatic cancer cells. Gastroenterology, 145(5), 1133–1143.e12.PubMedCrossRefGoogle Scholar
  142. Wang, P., Zhang, L., Chen, Z., & Meng, Z. (2013c). MicroRNA targets autophagy in pancreatic cancer cells during cancer therapy. Autophagy, 9(12), 2171–2172.PubMedCrossRefGoogle Scholar
  143. Wei, J., Ma, Z., Li, Y., Zhao, B., Wang, D., & Jin, Y. (2015). miR-143 inhibits cell proliferation by targeting autophagy-related 2B in non-small cell lung cancer H1299 cells. Molecular Medicine Reports, 11(1), 571–576.Google Scholar
  144. Weil, P. A. (2015). Regulation of gene expression. In V. W. Rodwell et al. (Eds.), Harper’s illustrated biochemistry, 30e. New York, NY: McGraw-Hill Education.Google Scholar
  145. Wilson, R. C., & Doudna, J. A. (2013). Molecular mechanisms of RNA interference. Annual Review of Biophysics, 42, 217–239.PubMedCrossRefGoogle Scholar
  146. Wu, H., Wang, F., Hu, S., Yin, C., Li, X., & Zhao, S. (2012). MiR-20a and miR-106b negatively regulate autophagy induced by leucine deprivation via suppression of ULK1 expression in C2C12 myoblasts. Cellular Signalling, 24(11), 2179–2186.PubMedCrossRefGoogle Scholar
  147. Wu, H. J., Pu, J. L., Krafft, P. R., Zhang, J. M., & Chen, S. (2015). The molecular mechanisms between autophagy and apoptosis: potential role in central nervous system disorders. Cellular and Molecular Neurobiology, 35(1), 85–99.PubMedCrossRefGoogle Scholar
  148. Xu, N., Zhang, J., Shen, C., Luo, Y., Xia, L., & Xue, F. (2012). Cisplatin-induced downregulation of miR-199a-5p increases drug resistance by activating autophagy in HCC cell. Biochemical and Biophysical Research Communications, 423(4), 826–831.PubMedCrossRefGoogle Scholar
  149. Xu, Y., An, Y., Wang, Y., Zhang, C., Zhang, H., & Huang, C. (2013). miR-101 inhibits autophagy and enhances cisplatin-induced apoptosis in hepatocellular carcinoma cells. Oncology Reports, 29(5), 2019–2024.PubMedGoogle Scholar
  150. Xu, L., Beckebaum, S., Iacob, S., Wu, G., Kaiser, G. M., & Radtke, A. (2014). MicroRNA-101 inhibits human hepatocellular carcinoma progression through EZH2 downregulation and increased cytostatic drug sensitivity. Journal of Hepatology, 60(3), 590–598.PubMedCrossRefGoogle Scholar
  151. Yang, Z., & Klionsky, D. J. (2010). Eaten alive: A history of macroautophagy. Nature Cell Biology, 12(9), 814–822.PubMedPubMedCentralCrossRefGoogle Scholar
  152. Yang, H., Kong, W., He, L., Zhao, J. J., O’Donnell, J. D., & Wang, J. (2008). MicroRNA expression profiling in human ovarian cancer: miR-214 induces cell survival and cisplatin resistance by targeting PTEN. Cancer Research, 68(2), 425–433.Google Scholar
  153. Yang, S., Wang, X., Contino, G., Liesa, M., Sahin, E., & Ying, H. (2011). Pancreatic cancers require autophagy for tumor growth. Genes and Development, 25(7), 717–729.PubMedPubMedCentralCrossRefGoogle Scholar
  154. Yang, Y., Liu, L., Zhang, Y., Guan, H., Wu, J., & Zhu, X. (2014). MiR-503 targets PI3K p85 and IKK-beta and suppresses progression of non-small cell lung cancer. International Journal of Cancer, 135(7), 1531–1542.PubMedCrossRefGoogle Scholar
  155. Yu, Y., Yang, L., Zhao, M., Zhu, S., Kang, R., & Vernon, P. (2012a). Targeting microRNA-30a-mediated autophagy enhances imatinib activity against human chronic myeloid leukemia cells. Leukemia, 26(8), 1752–1760.PubMedCrossRefGoogle Scholar
  156. Yu, Y., Cao, L., Yang, L., Kang, R., Lotze, M., & Tang, D. (2012b). microRNA 30A promotes autophagy in response to cancer therapy. Autophagy, 8(5), 853–855.PubMedPubMedCentralCrossRefGoogle Scholar
  157. Yu, L., Strandberg, L., & Lenardo, M. J. (2014). The selectivity of autophagy and its role in cell death and survival. Autophagy, 4(5), 567–573.CrossRefGoogle Scholar
  158. Yue, Z., Jin, S., Yang, C., Levine, A. J., & Heintz, N. (2003). Beclin 1, an autophagy gene essential for early embryonic development, is a haploinsufficient tumor suppressor. Proceedings of the National Academy of Sciences of the United States of America, 100(25), 15077–15082.PubMedPubMedCentralCrossRefGoogle Scholar
  159. Zhai, H., Fesler, A., & Ju, J. (2013a). MicroRNA: a third dimension in autophagy. Cell Cycle, 12(2), 246–250.PubMedPubMedCentralCrossRefGoogle Scholar
  160. Zhai, H., Song, B., Xu, X., Zhu, W., & Ju, J. (2013b). Inhibition of autophagy and tumor growth in colon cancer by miR-502. Oncogene, 32(12), 1570–1579.PubMedCrossRefGoogle Scholar
  161. Zhang, H., & Baehrecke, E. H. (2015). Eaten alive: Novel insights into autophagy from multicellular model systems. Trends in Cell Biology, 25(7), 376–387.PubMedPubMedCentralCrossRefGoogle Scholar
  162. Zhang, H., Tang, J., Li, C., Kong, J., Wang, J., & Wu, Y. (2015a). MiR-22 regulates 5-FU sensitivity by inhibiting autophagy and promoting apoptosis in colorectal cancer cells. Cancer Letters, 356(2 Pt B), 781–790.PubMedCrossRefGoogle Scholar
  163. Zhang, X., Shi, H., Lin, S., Ba, M., & Cui, S. (2015b). MicroRNA-216a enhances the radiosensitivity of pancreatic cancer cells by inhibiting beclin-1-mediated autophagy. Oncology Reports, 34(3), 1557–1564.PubMedGoogle Scholar
  164. Zhao, Y., & Srivastava, D. (2007). A developmental view of microRNA function. Trends in Biochemical Sciences, 32(4), 189–197.PubMedCrossRefGoogle Scholar
  165. Zhao, G., Zhang, J. G., Liu, Y., Qin, Q., Wang, B., Tian, K., et al. (2013). miR-148b functions as a tumor suppressor in pancreatic cancer by targeting AMPKalpha1. Molecular Cancer Therapeutics, 12(1), 83–93.PubMedCrossRefGoogle Scholar
  166. Zhao, N., Wang, R., Zhou, L., Zhu, Y., Gong, J., & Zhuang, S. M. (2014). MicroRNA-26b suppresses the NF-kappaB signaling and enhances the chemosensitivity of hepatocellular carcinoma cells by targeting TAK1 and TAB3. Molecular Cancer, 13, 35.PubMedPubMedCentralCrossRefGoogle Scholar
  167. Zhou, S., Zhao, L., Kuang, M., Zhang, B., Liang, Z., Yi, T., et al. (2012). Autophagy in tumorigenesis and cancer therapy: Dr. Jekyll or Mr. Hyde? Cancer Letters, 323(2), 115–127.PubMedCrossRefGoogle Scholar
  168. Zhu, H., Wu, H., Liu, X., Li, B., Chen, Y., Ren, X., et al. (2009). Regulation of autophagy by a beclin 1-targeted microRNA, miR-30a, in cancer cells. Autophagy, 5(6), 816–823.PubMedPubMedCentralCrossRefGoogle Scholar
  169. Zou, Z., Wu, L., Ding, H., Wang, Y., Zhang, Y., Chen, X., et al. (2012). MicroRNA-30a sensitizes tumor cells to cis-platinum via suppressing beclin 1-mediated autophagy. Journal of Biological Chemistry, 287(6), 4148–4156.PubMedCrossRefGoogle Scholar

Copyright information

© Springer International Publishing Switzerland 2016

Authors and Affiliations

  1. 1.Department of SurgeryDavis Heart and Lung Research Institute, The Ohio State University Wexner Medical CenterColumbusUSA
  2. 2.Department of PharmacologyThe Penn State Hershey Cancer Institute, The Pennsylvania State University, College of Medicine and Milton S. Hershey Medical CenterHersheyUSA

Personalised recommendations