An evaluation of the links between microRNA, autophagy, and epilepsy

Reviews in the Neurosciences

Volumn 26, Issue 2, 2015, Pages 225-237

  Gan, Jing ^a,b   Qu, Yi ^a,b   Li, Jiao ^a,b   Zhao, Fengyan ^a,b   Mu, Dezhi ^a,b,c  

^a SICHUAN UNIVERSITY   (China)

^b SICHUAN UNIVERSITY   (China)

^c UNIVERSITY OF CALIFORNIA   (United States)

Author keywords

autophagy; epilepsy; epileptogenesis; interactions; microRNA

Indexed keywords

MICRORNA;

APOPTOSIS; AUTOPHAGY; EPILEPSY; EPILEPTOGENESIS; HOMEOSTASIS; HUMAN; INFLAMMATION; NERVE CELL PLASTICITY; NONHUMAN; PRIORITY JOURNAL; REVIEW; ANIMAL; GENETICS; METABOLISM; SIGNAL TRANSDUCTION;

ANIMALS; AUTOPHAGY; EPILEPSY; HUMANS; MICRORNAS; SIGNAL TRANSDUCTION;

EID: 84926283985     PISSN: 03341763     EISSN: 21910200     Source Type: Journal    
DOI: 10.1515/revneuro-2014-0062     Document Type: Review

References (125)

1. Abdelmohsen, K., Srikantan, S., Tominaga, K., Kang, M.J., Yaniv, Y., Martindale, J.L., Yang, X., Park, S.S., Becker, K.G., Subramanian, M., et al. (2012). Growth inhibition by miR-519 via multiple p21-inducing pathways. Mol. Cell Biol. 32, 2530-2548.
2. Abraham, D., Jackson, N., Gundara, J.S., Zhao, J., Gill, A.J., Delbridge, L., Robinson, B.G., and Sidhu, S.B. (2011). MicroRNA profiling of sporadic and hereditary medullary thyroid cancer identifies predictors of nodal metastasis, prognosis, and potential therapeutic targets. Clin. Cancer Res. 17, 4772-4781.
3. Aguado, C., Sarkar, S., Korolchuk, V.I., Criado, O., Vernia, S., Boya, P., Sanz, P., de Cordoba, S.R., Knecht, E., and Rubinsztein, D.C. (2010). Laforin, the most common protein mutated in Lafora disease, regulates autophagy. Hum. Mol. Genet. 19, 2867-2876.
4. Alvarez-Erviti, L., Seow, Y., Schapira, A.H., Rodriguez-Oroz, M.C., Obeso, J.A., and Cooper, J.M. (2013). Influence of microRNA deregulation on chaperone-mediated autophagy and alpha-synuclein pathology in Parkinson's disease. Cell Death Dis. 4, e545.
5. Aronica, E., Fluiter, K., Iyer, A., Zurolo, E., Vreijling, J., van Vliet, E.A., Baayen, J.C., and Gorter, J.A. (2010). Expression pattern of miR-146a, an inflammation-associated microRNA, in experimental and human temporal lobe epilepsy. Eur. J. Neurosci. 31, 1100-1107.
6. Ashhab, M.U., Omran, A., Kong, H., Gan, N., He, F., Peng, J., and Yin, F. (2013). Expressions of tumor necrosis factor α and microRNA-155 in immature rat model of status epilepticus and children with mesial temporal lobe epilepsy. J. Mol. Neurosci. 51, 950-958.
7. Bartel, D.P. (2004). MicroRNAs: genomics, biogenesis, mechanism, and function. Cell 116, 281-297.
8. Berezikov, E., van Tetering, G., Verheul, M., van de Belt, J., van Laake, L., Vos, J., Verloop, R., van de Wetering, M., Guryev, V., and Takada, S. (2006). Many novel mammalian microRNA candidates identified by extensive cloning and RAKE analysis. Genome Res. 16, 1289-1298.
9. Bian, S. and Sun, T. (2011). Functions of noncoding RNAs in neural development and neurological diseases. Mol. Neurobiol. 44, 359-373.
10. Brest, P., Lapaquette, P., Souidi, M., Lebrigand, K., Cesaro, A., Vouret-Craviari, V., Mari, B., Barbry, P., Mosnier, J.F., Hebuterne, X., et al. (2011). A synonymous variant in IRGM alters a binding site for miR-196 and causes deregulation of IRGM-dependent xenophagy in Crohn's disease. Nat. Genet. 43, 242-245.
11. Cao, L., Chen, R., Xu, J., Lin, Y., Wang, R., and Chi, Z. (2009a). Vitamin E inhibits activated chaperone-mediated autophagy in rats with status epilepticus. Neuroscience 161, 73-77.
12. Cao, L., Xu, J., Lin, Y., Zhao, X., Liu, X., and Chi, Z. (2009b). Autophagy is upregulated in rats with status epilepticus and partly inhibited by vitamin E. Biochem. Biophys. Res. Commun. 379, 949-953.
13. Chang, B.S. and Lowenstein, D.H. (2003). Epilepsy. N. Engl. J. Med. 349, 1257-1266.
14. Chang, Y., Lin, J., and Tsung, A. (2012a). Manipulation of autophagy by MIR375 generates antitumor effects in liver cancer. Autophagy 8, 1833-1834.
15. Chang, Y., Yan, W., He, X., Zhang, L., Li, C., Huang, H., Nace, G., Geller, D.A., Lin, J., and Tsung, A. (2012b). miR-375 inhibits autophagy and reduces viability of hepatocellular carcinoma cells under hypoxic conditions. Gastroenterology 143, 187. e177-187.e178.
16. Chatterjee, A., Chattopadhyay, D., and Chakrabarti, G. (2014). miR-17-5p downregulation contributes to paclitaxel resistance of lung cancer cells through altering Beclin1 expression. PLoS One 9, e95716.
17. Chen, Y., Liersch, R., and Detmar, M. (2012). The miR-290-295 cluster suppresses autophagic cell death of melanoma cells. Sci. Rep. 2, 808.
18. Cheng, H.C., Kim, S.R., Oo, T.F., Kareva, T., Yarygina, O., Rzhetskaya, M., Wang, C., During, M., Talloczy, Z., Tanaka, K., et al. (2011). Akt suppresses retrograde degeneration of dopaminergic axons by inhibition of macroautophagy. J. Neurosci. 31, 2125-2135.
19. Christensen, M., Larsen, L.A., Kauppinen, S., and Schratt, G. (2009). Recombinant adeno-associated virus-mediated microRNA delivery into the postnatal mouse brain reveals a role for miR-134 in dendritogenesis in vivo. Front. Neural Circuits 3. doi: 10.3389/neuro.04.016.2009.
20. Christoforidis, S., Miaczynska, M., Ashman, K., Wilm, M., Zhao, L., Yip, S.C., Waterfield, M.D., Backer, J.M., and Zerial, M. (1999). Phosphatidylinositol-3-OH kinases are Rab5 effectors. Nat. Cell. Biol. 1, 249-252.
21. Codogno, P. and Meijer, A.J. (2005). Autophagy and signaling: their role in cell survival and cell death. Cell Death Differ. 12, 1509-1518.
22. Comincini, S., Allavena, G., Palumbo, S., Morini, M., Durando, F., Angeletti, F., Pirtoli, L., and Miracco, C. (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 Biol. Ther. 14, 574-586.
23. Coupe, B., Ishii, Y., Dietrich, M.O., Komatsu, M., Horvath, T.L., and Bouret, S.G. (2012). Loss of autophagy in pro-opiomelanocortin neurons perturbs axon growth and causes metabolic dysregulation. Cell Metab. 15, 247-255.
24. Criado, O., Aguado, C., Gayarre, J., Duran-Trio, L., Garcia-Cabrero, A.M., Vernia, S., San Millán, B., Heredia, M., Romá-Mateo, C., and Mouron, S. (2012). Lafora bodies and neurological defects in malin-deficient mice correlate with impaired autophagy. Hum. Mol. Genet. 21, 1521-1533.
25. Ding, Z., Wang, X., Schnackenberg, L., Khaidakov, M., Liu, S., Singla, S., Dai, Y., and Mehta, J.L. (2013). Regulation of autophagy and apoptosis in response to ox-LDL in vascular smooth muscle cells, and the modulatory effects of the microRNA hsa-let-7 g. Int. J. Cardiol. 168, 1378-1385.
26. Dong, Y., Wang, S., Zhang, T., Zhao, X., Liu, X., Cao, L., and Chi, Z. (2013). Ascorbic acid ameliorates seizures and brain damage in rats through inhibiting autophagy. Brain Res. 1535, 115-123.
27. Duran, J., Gruart, A., Garcia-Rocha, M., Delgado-Garcia, J.M., and Guinovart, J.J. (2014). Glycogen accumulation underlies neurodegeneration and autophagy impairment in Lafora disease. Hum. Mol. Genet. doi: 10.1093/hmg/ddu024.
28. Frankel, L.B., Wen, J., Lees, M., Hoyer-Hansen, M., Farkas, T., Krogh, A., Jaattela, M., and Lund, A.H. (2011). microRNA-101 is a potent inhibitor of autophagy. EMBO J. 30, 4628-4641.
29. Gibbings, D., Mostowy, S., Jay, F., Schwab, Y., Cossart, P., and Voinnet, O. (2012). Selective autophagy degrades DICER and AGO2 and regulates miRNA activity. Nat. Cell. Biol. 14, 1314-1321.
30. Gorter, J.A., Iyer, A., White, I., Colzi, A., van Vliet, E.A., Sisodiya, S., and Aronica, E. (2014). Hippocampal subregion-specific microRNA expression during epileptogenesis in experimental temporal lobe epilepsy. Neurobiol. Dis. 62, 508-520.
31. Goto, J., Talos, D.M., Klein, P., Qin, W., Chekaluk, Y.I., Anderl, S., Malinowska, I.A., Di Nardo, A., Bronson, R.T., Chan, J.A., et al. (2011). Regulable neural progenitor-specific Tsc1 loss yields giant cells with organellar dysfunction in a model of tuberous sclerosis complex. Proc. Natl. Acad. Sci. USA 108, E1070-E1079.
32. Gwak, H.S., Kim, T.H., Jo, G.H., Kim, Y.J., Kwak, H.J., Kim, J.H., Yin, J., Yoo, H., Lee, S.H., and Park, J.B. (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, e47449.
33. Harris, H. and Rubinsztein, D.C. (2012). Control of autophagy as a therapy for neurodegenerative disease. Nat. Rev. Neurol. 8, 108-117.
34. Henshall, D.C. (2013). MicroRNAs in the pathophysiology and treatment of status epilepticus. Front. Mol. Neurosci. 6, 37.
35. Hermeking, H. (2010). The miR-34 family in cancer and apoptosis. Cell. Death Differ. 17, 193-199.
36. Hernandez, D., Torres, C.A., Setlik, W., Cebrian, C., Mosharov, E.V., Tang, G., Cheng, H.C., Kholodilov, N., Yarygina, O., Burke, R.E., et al. (2012). Regulation of presynaptic neurotransmission by macroautophagy. Neuron 74, 277-284.
37. Hu, K., Zhang, C., Long, L., Long, X., Feng, L., Li, Y., and Xiao, B. (2011). Expression profile of microRNAs in rat hippocampus following lithium-pilocarpine-induced status epilepticus. Neurosci. Lett. 488, 252-257.
38. Hu, K., Xie, Y.-Y., Zhang, C., Ouyang, D.-S., Long, H.-Y., Sun, D.-N., Long, L.-L., Feng, L., Li, Y., and Xiao, B. (2012). MicroRNA expression profile of the hippocampus in a rat model of temporal lobe epilepsy and miR-34a-targeted neuroprotection against hippocampal neurone cell apoptosis post-status epilepticus. BMC Neurosci. 13, 115.
39. Huang, Y., Chuang, A.Y., and Ratovitski, E.A. (2011). Phospho-deltaNp63alpha/miR-885-3p axis in tumor cell life and cell death upon cisplatin exposure. Cell Cycle 10, 3938-3947.
40. Huang, Y., Guerrero-Preston, R., and Ratovitski, E.A. (2012). Phospho-deltaNp63alpha-dependent regulation of autophagic signaling through transcription and micro-RNA modulation. Cell Cycle 11, 1247-1259.
41. Iyer, A., Zurolo, E., Prabowo, A., Fluiter, K., Spliet, W.G., van Rijen, P.C., Gorter, J.A., and Aronica, E. (2012). MicroRNA-146a: a key regulator of astrocyte-mediated inflammatory response. PLoS One 7, e44789.
42. Jegga, A.G., Schneider, L., Ouyang, X., and Zhang, J. (2011). Systems biology of the autophagy-lysosomal pathway. Autophagy 7, 477-489.
43. Jimenez-Mateos, E.M., Engel, T., Merino-Serrais, P., McKiernan, R.C., Tanaka, K., Mouri, G., Sano, T., O'Tuathaigh, C., Waddington, J.L., Prenter, S., et al. (2012). Silencing microRNA-134 produces neuroprotective and prolonged seizure-suppressive effects. Nat. Med. 18, 1087-1094.
44. Kan, A.A., van Erp, S., Derijck, A.A., de Wit, M., Hessel, E.V., O'Duibhir, E., de Jager, W., Van Rijen, P.C., Gosselaar, P.H., de Graan, P.E., et al. (2012). Genome-wide microRNA profiling of human temporal lobe epilepsy identifies modulators of the immune response. Cell. Mol. Life Sci. 69, 3127-3145.
45. Kim, V.N., Han, J., and Siomi, M.C. (2009). Biogenesis of small RNAs in animals. Nat. Rev. Mol. Cell Biol. 10, 126-139.
46. Klionsky, D.J. (2007). Autophagy: from phenomenology to molecular understanding in less than a decade. Nat. Rev. Mol. Cell Biol. 8, 931-937.
47. Korkmaz, G., le Sage, C., Tekirdag, K.A., Agami, R., and Gozuacik, D. (2012). miR-376b controls starvation and mTOR inhibition-related autophagy by targeting ATG4C and BECN1. Autophagy 8, 165-176.
48. Korkmaz, G., Tekirdag, K.A., Ozturk, D.G., Kosar, A., Sezerman, O.U., and Gozuacik, D. (2013). MIR376A is a regulator of starvation-induced autophagy. PLoS One 8, e82556.
49. Kovaleva, V., Mora, R., Park, Y.J., Plass, C., Chiramel, A.I., Bartenschlager, R., Dohner, H., Stilgenbauer, S., Pscherer, A., Lichter, P., et al. (2012). miRNA-130a targets ATG2B and DICER1 to inhibit autophagy and trigger killing of chronic lymphocytic leukemia cells. Cancer Res. 72, 1763-1772.
50. Krichevsky, A.M., Sonntag, K.C., Isacson, O., and Kosik, K.S. (2006). Specific microRNAs modulate embryonic stem cell-derived neurogenesis. Stem cells 24, 857-864.
51. Lagos-Quintana, M., Rauhut, R., Yalcin, A., Meyer, J., Lendeckel, W., and Tuschl, T. (2002). Identification of tissue-specific microRNAs from mouse. Curr. Biol. 12, 735-739.
52. Lan, S.H., Wu, S.Y., Zuchini, R., Lin, X.Z., Su, I.J., Tsai, T.F., Lin, Y.J., Wu, C.T., and Liu, H.S. (2014). Autophagy suppresses tumorigenesis of hepatitis B virus-associated hepatocellular carcinoma through degradation of microRNA-224. Hepatology 59, 505-517.
53. 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.
54. Levine, B. and Klionsky, D.J. (2004). Development by self-digestion: molecular mechanisms and biological functions of autophagy. Dev. Cell 6, 463-477.
55. Li, M.M., Li, X.M., Zheng, X.P., Yu, J.T., and Tan, L. (2014). MicroRNAs dysregulation in epilepsy. Brain Res. 1584, 94-104.
56. Li, Q., Xie, J., Li, R., Shi, J., Sun, J., Gu, R., Ding, L., Wang, L. & Xu, B. (2014). Overexpression of microRNA-99a attenuates heart remodelling and improves cardiac performance after myocardial infarction. J Cell Mol Med. 18, 919-928.
57. Liu, K. (2013). miR-34a regulates autophagy and chemotherapeutic response in retinoblastoma cells through repression of HMGB1. Doctoral Thesis, Central South University.
58. Lu, C., Chen, J., Xu, H.G., Zhou, X., He, Q., Li, Y.L., Jiang, G., Shan, Y., Xue, B., Zhao, R.X., et al. (2014). MIR106B and MIR93 prevent removal of bacteria from epithelial cells by disrupting ATG16L1-mediated autophagy. Gastroenterology 146, 188-199.
59. Luciano, D.J., Mirsky, H., Vendetti, N.J., and Maas, S. (2004). RNA editing of a miRNA precursor. RNA 10, 1174-1177.
60. Magill, S.T., Cambronne, X.A., Luikart, B.W., Lioy, D.T., Leighton, B.H., Westbrook, G.L., Mandel, G., and Goodman, R.H. (2010). microRNA-132 regulates dendritic growth and arborization of newborn neurons in the adult hippocampus. P. Natl. Acad. Sci. 107, 20382-20387.
61. Massey, D.C. and Parkes, M. (2007). Genome-wide association scanning highlights two autophagy genes, ATG16L1 and IRGM, as being significantly associated with Crohn's disease. Autophagy 3, 649-651.
62. McKiernan, R.C., Jimenez-Mateos, E.M., Sano, T., Bray, I., Stallings, R.L., Simon, R.P., and Henshall, D.C. (2012). Expression profiling the microRNA response to epileptic preconditioning identifies miR-184 as a modulator of seizure-induced neuronal death. Exp. Neurol. 237, 346-354.
63. McMahon, J., Huang, X., Yang, J., Komatsu, M., Yue, Z., Qian, J., Zhu, X., and Huang, Y. (2012). Impaired autophagy in neurons after disinhibition of mammalian target of rapamycin and its contribution to epileptogenesis. J. Neurosci. 32, 15704-15714.
64. McNamara, J.O., Huang, Y.Z., and Leonard, A.S. (2006). Molecular signaling mechanisms underlying epileptogenesis. Sci. Signal. 2006, re12.
65. Meenhuis, A., van Veelen, P.A., de Looper, H., van Boxtel, N., van den Berge, I.J., Sun, S.M., Taskesen, E., Stern, P., de Ru, A.H., van Adrichem, A.J., et al. (2011). MiR-17/20/93/106 promote hematopoietic cell expansion by targeting sequestosome 1-regulated pathways in mice. Blood 118, 916-925.
66. Mikhaylova, O., Stratton, Y., Hall, D., Kellner, E., Ehmer, B., Drew, A.F., Gallo, C.A., Plas, D. R., Biesiada, J., Meller, J., et al. (2012). VHL-regulated MiR-204 suppresses tumor growth through inhibition of LC3B-mediated autophagy in renal clear cell carcinoma. Cancer Cell 21, 532-546.
67. Miller, T.E., Ghoshal, K., Ramaswamy, B., Roy, S., Datta, J., Shapiro, C.L., Jacob, S., and Majumder, S. (2008). MicroRNA-221/222 confers tamoxifen resistance in breast cancer by targeting p27Kip1. J. Biol. Chem. 283, 29897-29903.
68. Nguyen, H.T., Dalmasso, G., Muller, S., Carriere, J., Seibold, F., and Darfeuille-Michaud, A. (2014). Crohn's disease-associated adherent invasive Escherichia coli modulate levels of microRNAs in intestinal epithelial cells to reduce autophagy. Gastroenterology 146, 508-519.
69. Ni, H., Feng, X., Gong, Y., Tao, L.Y., and Wu, X.R. (2011). Acute phase expression pattern of ZnTs, LC3, and beclin-1 in rat Hippocampus and its regulation by 3-methyladenine following recurrent neonatal seizures. Biol. Trace Elem. Res. 143, 320-331.
70. Ni, H., Yan, J.Z., Zhang, L.L., Feng, X., and Wu, X.R. (2012). Long-term effects of recurrent neonatal seizures on neurobehavioral function and related gene expression and its intervention by inhibitor of cathepsin B. Neurochem. Res. 37, 31-39.
71. Nilsson, P. and Saido, T.C. (2014). Dual roles for autophagy: degradation and secretion of Alzheimer's disease Abeta peptide. Bioessays 36, 570-578.
72. Nudelman, A.S., DiRocco, D.P., Lambert, T.J., Garelick, M.G., Le, J., Nathanson, N.M., and Storm, D.R. (2010). Neuronal activity rapidly induces transcription of the CREB-regulated microRNA-132, in vivo. Hippocampus 20, 492-498.
73. Obernosterer, G., Leuschner, P.J., Alenius, M., and Martinez, J. (2006). Post-transcriptional regulation of microRNA expression. RNA 12, 1161-1167.
74. Omran, A., Peng, J., Zhang, C., Xiang, Q.L., Xue, J., Gan, N., Kong, H., and Yin, F. (2012). Interleukin-1beta and microRNA-146a in an immature rat model and children with mesial temporal lobe epilepsy. Epilepsia 53, 1215-1224.
75. Palumbo, S., Miracco, C., Pirtoli, L., and Comincini, S. (2014). Emerging roles of microRNA in modulating cell-death processes in malignant glioma. J. Cell. Physiol. 229, 277-286.
76. Pavlides, S., Tsirigos, A., Migneco, G., Whitaker-Menezes, D., Chiavarina, B., Flomenberg, N., Frank, P.G., Casimiro, M.C., Wang, C., Pestell, R.G., et al. (2010). The autophagic tumor stroma model of cancer: role of oxidative stress and ketone production in fueling tumor cell metabolism. Cell Cycle 9, 3485-3505.
77. Peng, J., Omran, A., Ashhab, M.U., Kong, H., Gan, N., He, F., and Yin, F. (2013). Expression patterns of miR-124, miR-134, miR-132, and miR-21 in an immature rat model and children with mesial temporal lobe epilepsy. J. Mol. Neurosci. 50, 291-297.
78. Pennati, M., Lopergolo, A., Profumo, V., De Cesare, M., Sbarra, S., Valdagni, R., Zaffaroni, N., Gandellini, P., and Folini, M. (2014). miR-205 impairs the autophagic flux and enhances cisplatin cytotoxicity in castration-resistant prostate cancer cells. Biochem. Pharmacol. 87, 579-597.
79. Pitkänen, A. and Lukasiuk, K. (2011). Mechanisms of epileptogenesis and potential treatment targets. Lancet Neurol. 10, 173-186.
80. Puri, R., Suzuki, T., Yamakawa, K., and Ganesh, S. (2012). Dysfunctions in endosomal-lysosomal and autophagy pathways underlie neuropathology in a mouse model for Lafora disease. Hum. Mol. Genet. 21, 175-184.
81. Qased, A.B., Yi, H., Liang, N., Ma, S., Qiao, S., and Liu, X. (2013). MicroRNA-18a upregulates autophagy and ataxia telangiectasia mutated gene expression in HCT116 colon cancer cells. Mol. Med. Rep. 7, 559-564.
82. Raver-Shapira, N., Marciano, E., Meiri, E., Spector, Y., Rosenfeld, N., Moskovits, N., Bentwich, Z., and Oren, M. (2007). Transcriptional activation of miR-34a contributes to p53-mediated apoptosis. Mol. Cell 26, 731-743.
83. Ravikumar, B., Imarisio, S., Sarkar, S., O'Kane, C.J., and Rubinsztein, D.C. (2008). Rab5 modulates aggregation and toxicity of mutant huntingtin through macroautophagy in cell and fly models of Huntington disease. J. Cell. Sci. 121, 1649-1660.
84. Ravikumar, B., Futter, M., Jahreiss, L., Korolchuk, V.I., Lichtenberg, M., Luo, S., Massey, D.C., Menzies, F.M., Narayanan, U., Renna, M., et al. (2009). Mammalian macroautophagy at a glance. J. Cell. Sci. 122, 1707-1711.
85. Risbud, R.M., Lee, C., and Porter, B.E. (2011). Neurotrophin-3 mRNA a putative target of miR21 following status epilepticus. Brain Res. 1424, 53-59.
86. Roccaro, A.M., Sacco, A., Jia, X., Azab, A.K., Maiso, P., Ngo, H.T., Azab, F., Runnels, J., Quang, P., and Ghobrial, I.M. (2010). microRNA-dependent modulation of histone acetylation in Waldenstrom macroglobulinemia. Blood 116, 1506-1514.
87. Ryu, H.J., Kim, J.E., Yeo, S.I., and Kang, T.C. (2011). p65/RelA-Ser529 NF-kappaB subunit phosphorylation induces autophagic astroglial death (Clasmatodendrosis) following status epilepticus. Cell. Mol. Neurobiol. 31, 1071-1078.
88. Sano, T., Reynolds, J.P., Jimenez-Mateos, E.M., Matsushima, S., Taki, W. and Henshall, D.C. (2012). MicroRNA-34a upregulation during seizure-induced neuronal death. Cell Death Dis. 3, e287.
89. Schratt, G.M., Tuebing, F., Nigh, E.A., Kane, C.G., Sabatini, M.E., Kiebler, M., and Greenberg, M.E. (2006). A brain-specific microRNA regulates dendritic spine development. Nature 439, 283-289.
90. Shacka, J.J., Lu, J., Xie, Z.L., Uchiyama, Y., Roth, K.A., and Zhang, J. (2007). Kainic acid induces early and transient autophagic stress in mouse hippocampus. Neurosci Lett. 414, 57-60.
91. Shahbazi, J., Lock, R., and Liu, T. (2013). Tumor protein 53-induced nuclear protein 1 enhances p53 function and represses tumorigenesis. Front Genet. 4, 80.
92. Shen, W. and Ganetzky, B. (2009). Autophagy promotes synapse development in Drosophila. J. Cell. Biol. 187, 71-79.
93. Shi, G., Shi, J., Liu, K., Liu, N., Wang, Y., Fu, Z., Ding, J., Jia, L., and Yuan, W. (2013). Increased miR-195 aggravates neuropathic pain by inhibiting autophagy following peripheral nerve injury. Glia 61, 504-512.
94. Shintani, T. and Klionsky, D.J. (2004). Autophagy in health and disease: a double-edged sword. Science 306, 990-995.
95. Singh, P.K., Singh, S., and Ganesh, S. (2013). Activation of serum/glucocorticoid-induced kinase 1 (SGK1) underlies increased glycogen levels, mTOR activation, and autophagy defects in Lafora disease. Mol. Biol. Cell 24, 3776-3786.
96. Solaz-Fuster, M.C., Gimeno-Alcaniz, J.V., Ros, S., Fernandez-Sanchez, M.E., Garcia-Fojeda, B., Criado Garcia, O., Vilchez, D., Dominguez, J., Garcia-Rocha, M., Sanchez-Piris, M., et al. (2008). Regulation of glycogen synthesis by the laforin-malin complex is modulated by the AMP-activated protein kinase pathway. Hum. Mol. Genet. 17, 667-678.
97. Song, Y.-j., Tian, X.-b., Zhang, S., Zhang, Y.-x., Li, X., Li, D., Cheng, Y., Zhang, J.-n., Kang, C.-s., and Zhao, W. (2011). Temporal lobe epilepsy induces differential expression of hippocampal miRNAs including let-7e and miR-23a/b. Brain Res. 1387, 134-140.
98. Tang, B., Li, N., Gu, J., Zhuang, Y., Li, Q., Wang, H.G., Fang, Y., Yu, B., Zhang, J.Y., Xie, Q.H., et al. (2012). Compromised autophagy by MIR30B benefits the intracellular survival of Helicobacter pylori. Autophagy 8, 1045-1057.
99. Tarasov, V., Jung, P., Verdoodt, B., Lodygin, D., Epanchintsev, A., Menssen, A., Meister, G., and Hermeking, H. (2007). Differential regulation of microRNAs by p53 revealed by massively parallel sequencing. Cell Cycle 6, 1586-1593.
100. Tazawa, H., Yano, S., Yoshida, R., Yamasaki, Y., Sasaki, T., Hashimoto, Y., Kuroda, S., Ouchi, M., Onishi, T., Uno, F., et al. (2012). Genetically engineered oncolytic adenovirus induces autophagic cell death through an E2F1-microRNA-7-epidermal growth factor receptor axis. Int. J. Cancer 131, 2939-2950.
101. Tivnan, A., Tracey, L., Buckley, P.G., Alcock, L.C., Davidoff, A.M., and Stallings, R.L. (2011). MicroRNA-34a is a potent tumor suppressor molecule in vivo in neuroblastoma. BMC cancer 11, 33.
102. nd Annual Meeting and Exposition, Orlando, FL.
103. Ucar, A., Gupta, S.K., Fiedler, J., Erikci, E., Kardasinski, M., Batkai, S., Dangwal, S., Kumarswamy, R., Bang, C., Holzmann, A., et al. (2012). The miRNA-212/132 family regulates both cardiac hypertrophy and cardiomyocyte autophagy. Nat. Commun. 3, 1078.
104. Vasudevan, S., Tong, Y., and Steitz, J.A. (2007). Switching from repression to activation: microRNAs can up-regulate translation. Science 318, 1931-1934.
105. Vermeulen, A., Robertson, B., Dalby, A.B., Marshall, W.S., Karpilow, J., Leake, D., Khvorova, A., and Baskerville, S. (2007). Double-stranded regions are essential design components of potent inhibitors of RISC function. RNA 13, 723-730.
106. Wan, G., Xie, W., Liu, Z., Xu, W., Lao, Y., Huang, N., Cui, K., Liao, M., He, J., Jiang, Y., et al. (2014). Hypoxia-induced MIR155 is a potent autophagy inducer by targeting multiple players in the MTOR pathway. Autophagy 10, 70-79.
107. Wang, K. and Klionsky, D.J. (2011). Mitochondria removal by autophagy. Autophagy 7, 297-300.
108. Wang, S.Y., Yu, Q.J., Zhang, R.D., and Liu, B. (2011). Core signaling pathways of survival/death in autophagy-related cancer networks. Int. J. Biochem. Cell Biol. 43, 1263-1266.
109. Wang, J., Yang, K., Zhou, L., Minhaowu, Wu, Y., Zhu, M., Lai, X., Chen, T., Feng, L., Li, M., et al. (2013a). MicroRNA-155 promotes autophagy to eliminate intracellular mycobacteria by targeting Rheb. PLoS Pathog. 9, e1003697.
110. Wang, P., Zhang, J., Zhang, L., Zhu, Z., Fan, J., Chen, L., Zhuang, L., Luo, J., Chen, H., Liu, L., et al. (2013b). MicroRNA 23b regulates autophagy associated with radioresistance of pancreatic cancer cells. Gastroenterology 145, 1133.e12-1143.e12.
111. Welch, C., Chen, Y., and Stallings, R. (2007). MicroRNA-34a functions as a potential tumor suppressor by inducing apoptosis in neuroblastoma cells. Oncogene 26, 5017-5022.
112. Wong, M. (2010). Mammalian target of rapamycin (mTOR) inhibition as a potential antiepileptogenic therapy: from tuberous sclerosis to common acquired epilepsies. Epilepsia 51, 27-36.
113. Wu, H., Wang, F., Hu, S., Yin, C., Li, X., Zhao, S., Wang, J., and Yan, X. (2012). MiR-20a and miR-106b negatively regulate autophagy induced by leucine deprivation via suppression of ULK1 expression in C2C12 myoblasts. Cell Signal. 24, 2179-2186.
114. Xiao, J., Zhu, X., He, B., Zhang, Y., Kang, B., Wang, Z., and Ni, X. (2011). MiR-204 regulates cardiomyocyte autophagy induced by ischemia-reperfusion through LC3-II. J. Biomed. Sci. 18, 35.
115. Xu, N., Zhang, J., Shen, C., Luo, Y., Xia, L., Xue, F., and Xia, Q. (2012). Cisplatin-induced downregulation of miR-199a-5p increases drug resistance by activating autophagy in HCC cell. Biochem. Biophys. Res. Commun. 423, 826-831.
116. Xu, Q., Meng, S., Liu, B., Li, M.Q., Li, Y., Fang, L., and Li, Y.G. (2014a). MicroRNA-130a regulates autophagy of endothelial progenitor cells through Runx3. Clin. Exp. Pharmacol. Physiol. 41, 351-357.
117. Xu, X., Fu, Y., Tong, J., Fan, S., Xu, K., Sun, H., Liang, Y., Yan, C., Yuan, Z., and Ge, Y. (2014b). MicroRNA-216b/Beclin 1 axis regulates autophagy and apoptosis in human Tenon's capsule fibroblasts upon hydroxycamptothecin exposure. Exp. Eye Res. 123c, 43-55.
118. Yang, J., Chen, D., He, Y., Melendez, A., Feng, Z., Hong, Q., Bai, X., Li, Q., Cai, G., Wang, J., et al. (2013a). MiR-34 modulates Caenorhabditis elegans lifespan via repressing the autophagy gene atg9. Age (Dordr) 35, 11-22.
119. Yang, X., Zhong, X., Tanyi, J.L., Shen, J., Xu, C., Gao, P., Zheng, T.M., DeMichele, A., and Zhang, L. (2013b). mir-30d Regulates multiple genes in the autophagy pathway and impairs autophagy process in human cancer cells. Biochem. Biophys. Res. Commun. 431, 617-622.
120. You, G., Yan, W., Zhang, W., Wang, Y., Bao, Z., Li, S., Li, G., Song, Y., Kang, C., and Jiang, T. (2012). Significance of miR-196b in tumor-related epilepsy of patients with gliomas. PloS one 7, e46218.
121. Yu, Y., Yang, L., Zhao, M., Zhu, S., Kang, R., Vernon, P., Tang, D., and Cao, L. (2012). Targeting microRNA-30a-mediated autophagy enhances imatinib activity against human chronic myeloid leukemia cells. Leukemia 26, 1752-1760.
122. Zhai, H., Song, B., Xu, X., Zhu, W., and Ju, J. (2013a). Inhibition of autophagy and tumor growth in colon cancer by miR-502. Oncogene 32, 1570-1579.
123. Zhai, Z., Wu, F., Chuang, A.Y., and Kwon, J.H. (2013b). miR-106b fine tunes ATG16L1 expression and autophagic activity in intestinal epithelial HCT116 cells. Inflamm. Bowel Dis. 19, 2295-2301.
124. Zhai, Z., Wu, F., Dong, F., Chuang, A.Y., Messer, J.S., Boone, D.L., and Kwon, J.H. (2014). Human autophagy gene ATG16L1 is post-transcriptionally regulated by MIR142-3p. Autophagy 10, 468-479.
125. Zhu, H., Wu, H., Liu, X., Li, B., Chen, Y., Ren, X., Liu, C.-G., and Yang, J.-M. (2009). Regulation of autophagy by a beclin 1-targeted microRNA, miR-30a, in cancer cells. Autophagy 5, 816-823.