mRNA and miRNA regulatory networks reflective of multi-walled carbon nanotube-induced lung inflammatory and fibrotic pathologies in mice

Toxicological Sciences

Volumn 144, Issue 1, 2015, Pages 51-64

  Dymacek, Julian ^a   Snyder Talkington, Brandi N ^b   Porter, Dale W ^b   Mercer, Robert R ^b   Wolfarth, Michael G ^b   Castranova, Vincent ^c   Qian, Yong ^b   Guo, Nancy L ^c  

^a West Virginia University   (United States)

^b NATIONAL INSTITUTE FOR OCCUPATIONAL SAFETY AND HEALTH   (United States)

^c WEST VIRGINIA UNIVERSITY   (United States)

Author keywords

microRNA; mRNA; Multi walled carbon nanotubes

Indexed keywords

MESSENGER RNA; MICRORNA; MULTI WALLED NANOTUBE; AUTACOID; CARBON NANOTUBE; GENETIC MARKER;

ANIMAL EXPERIMENT; ANIMAL MODEL; ARTICLE; GENE EXPRESSION PROFILING; LUNG ASPIRATION; LUNG FIBROSIS; LUNG LAVAGE; MALE; MICROARRAY ANALYSIS; MOUSE; NONHUMAN; PATHOGENESIS; PNEUMONIA; RNA EXTRACTION; TIME SERIES ANALYSIS; ANIMAL; BIOLOGY; C57BL MOUSE; CHEMICALLY INDUCED; DISEASE MODEL; EXPOSURE; GENE EXPRESSION REGULATION; GENE REGULATORY NETWORK; GENETIC DATABASE; GENETIC MARKER; GENETICS; LUNG; METABOLISM; PATHOLOGY; TIME;

MUS;

ANIMALS; COMPUTATIONAL BIOLOGY; DATABASES, GENETIC; DISEASE MODELS, ANIMAL; GENE EXPRESSION PROFILING; GENE EXPRESSION REGULATION; GENE REGULATORY NETWORKS; GENETIC MARKERS; INFLAMMATION MEDIATORS; INHALATION EXPOSURE; LUNG; MALE; MICE, INBRED C57BL; MICRORNAS; NANOTUBES, CARBON; PNEUMONIA; PULMONARY FIBROSIS; RNA, MESSENGER; TIME FACTORS;

EID: 84924463120     PISSN: 10966080     EISSN: 10960929     Source Type: Journal    
DOI: 10.1093/toxsci/kfu262     Document Type: Article

References (90)

1. Auerbach, O., Garfinkel, L., and Parks, V. R. (1979). Scar cancer of the lung: increase over a 21 year period. Cancer 43, 636-642.
2. Avraham, R., and Yarden, Y. (2012). Regulation of signalling by microRNAs. Biochem. Soc. Trans. 40, 26-30.
3. Bartel, D. P. (2004). MicroRNAs: genomics, biogenesis, mechanism, and function. Cell 116, 281-297.
4. Beezhold, K. J., Castranova, V., and Chen, F. (2010). Microprocessor of microRNAs: regulation and potential for therapeutic intervention. Mol. Cancer 9, 134.
5. Bjoraker, J. A., Ryu, J. H., Edwin, M. K., Myers, J. L., Tazelaar, H. D., Schroeder, D. R., and Offord, K. P. (1998). Prognostic significance of histopathologic subsets in idiopathic pulmonary fibrosis. Am. J. Respir. Crit. Care Med. 157, 199-203.
6. Bockhorn, J.,Yee,K., Chang, Y. F., Prat, A.,Huo,D.,Nwachukwu, C., Dalton, R., Huang, S., Swanson, K. E., Perou, C.M., et al. (2013). MicroRNA-30c targets cytoskeleton genes involved in breast cancer cell invasion. Breast Cancer Res. Treat. 137, 373-382.
7. Brock, M., Trenkmann, M., Gay, R. E., Michel, B. A., Gay, S., Fischler, M., Ulrich, S., Speich, R., and Huber, L. C. (2009). Interleukin-6 modulates the expression of the bone morphogenic protein receptor type II through a novel STAT3-microRNA cluster 17/92 pathway. Circ. Res. 104, 1184-1191.
8. Brown, T. A. (2006). Genomes, 3rd ed. pp. 14-18. Garland Science, New York.
9. Chen, X., Hu, Z., Wang, W., Ba, Y., Ma, L., Zhang, C., Wang, C., Ren, Z., Zhao, Y., Wu, S., et al. (2012). Identification of ten serum microRNAs from a genome-wide serum microRNA expression profile as novel noninvasive biomarkers for nonsmall cell lung cancer diagnosis. Int. J. Cancer 130, 1620-1628.
10. Cheng, C., and Li, L. M. (2008). Inferring microRNA activities by combining gene expression with microRNA target prediction. PLoS One 3, e1989.
11. Chi, S. W., Zang, J. B., Mele, A., and Darnell, R. B. (2009). Argonaute HITS-CLIP decodes microRNA-mRNA interaction maps. Nature 460, 479-486.
12. Cho, J. H., Gelinas, R., Wang, K., Etheridge, A., Piper, M. G., Batte, K., Dakhallah, D., Price, J., Bornman, D., Zhang, S., et al. (2011). Systems biology of interstitial lung diseases: integration of mRNA and microRNA expression changes. BMC Med. Genomics 4, 8.
13. Dews, M., Fox, J. L., Hultine, S., Sundaram, P., Wang, W., Liu, Y. Y., Furth, E., Enders, G. H., El-Deiry, W., Schelter, J. M., et al. (2010). The myc-miR-17~92 axis blunts TGF β signaling and production of multiple TGF β-dependent antiangiogenic factors. Cancer Res. 70, 8233-8246.
14. Dey, B. K., Gagan, J., Yan, Z., and Dutta, A. (2012). miR-26a is required for skeletal muscle differentiation and regeneration in mice. Genes Dev. 26, 2180-2191.
15. Donaldson, K., Aitken, R., Tran, L., Stone, V., Duffin, R., Forrest, G., and Alexander, A. (2006). Carbon nanotubes: a review of their properties in relation to pulmonary toxicology and workplace safety. Toxicol. Sci. 92, 5-22.
16. Douglas, W. W., Ryu, J. H., Swensen, S. J., Offord, K. P., Schroeder, D. R., Caron, G. M., and DeRemee, R. A. (1998). Colchicine versus prednisone in the treatment of idiopathic pulmonary fibrosis. A randomized prospective study. Members of the Lung Study Group. Am. J. Respir. Crit. Care Med. 158, 220-225.
17. Dymacek, J., and Guo, N. L. (2011). Systems approach to identifying relevant pathways from phenotype information in dosedependent time series microarray data. Proceedings of 2011 IEEE International Conference on Bioinformatics and Biomedicine, pp. 290-293. IEEE Computer Society, Washington, DC.
18. Dymacek, J., and Guo, N. L. (2014). Integrated miRNA and mRNA analysis of time series microarray data. Proceedings of the 5th ACM Conference on Bioinformatics, Computational Biology, and Health Informatics. pp. 122-127. ACM New York, NY, USA.
19. EPA. (2014). United States environmental protection agency computational toxicology research. http://www.epa.gov/ncct/, Accessed June 6, 2014.
20. Fatica, A., and Bozzoni, I. (2014). Long non-coding RNAs: new players in cell differentiation and development. Nat. Rev. Genetics 15, 7-21.
21. Ferte, C., Trister, A. D., Huang, E., Bot, B. M., Guinney, J., Commo, F., Sieberts, S., Andre, F., Besse, B., Soria, J. C., et al. (2013). Impact of bioinformatic procedures in the development and translation of high-throughput molecular classifiers in oncology. Clin. Cancer Res. 19, 4315-4325.
22. Flaherty, K. R., Travis, W. D., Colby, T. V., Toews, G. B., Kazerooni, E. A., Gross, B. H., Jain, A., Strawderman, R. L., Flint, A., Lynch, J. P., et al. (2001). Histopathologic variability in usual and nonspecific interstitial pneumonias. Am. J. Respir. Crit. Care Med. 164, 1722-1727.
23. Gabriely, G., Wurdinger, T., Kesari, S., Esau, C. C., Burchard, J., Linsley, P. S., and Krichevsky, A. M. (2008). MicroRNA 21 promotes glioma invasion by targeting matrix metalloproteinase regulators. Mol. Cell. Biol. 28, 5369-5380.
24. Griffiths-Jones, S., Grocock, R. J., van Dongen, S., Bateman, A., and Enright, A. J. (2006). miRBase: microRNA sequences, targets and gene nomenclature. Nucleic Acids Res. 34, D140-D144.
25. Guo, N. L., Wan, Y. W., Denvir, J., Porter, D. W., Pacurari, M., Wolfarth, M. G., Castranova, V., and Qian, Y. (2012). Multiwalled carbon nanotube-induced gene signatures in the mouse lung: potential predictive value for human lung cancer risk and prognosis. J. Toxicol. Environ. Health Part A 75, 1129-1153.
26. Hafner, M., Landthaler, M., Burger, L., Khorshid, M., Hausser, J., Berninger, P., Rothballer, A., Ascano, M., Jr, Jungkamp, A. C., Munschauer, M., et al. (2010). Transcriptome-wide identification of RNA-binding protein and microRNA target sites by PAR-CLIP. Cell 141, 129-141.
27. Helwak, A., Kudla, G., Dudnakova, T., and Tollervey, D. (2013). Mapping the human miRNA interactome by CLASH reveals frequent noncanonical binding. Cell 153, 654-665.
28. Hofmann, M. H., Heinrich, J., Radziwill, G., and Moelling, K. (2009). A short hairpin DNA analogous to miR-125b inhibits C-Raf expression, proliferation, and survival of breast cancer cells. Mol. Cancer Res. 7, 1635-1644.
29. Homer, R. J., Elias, J. A., Lee, C. G., and Herzog, E. (2011). Modern concepts on the role of inflammation in pulmonary fibrosis. Arch. Pathol. Lab. Med. 135, 780-788.
30. Hoo, Z. H., and Whyte, M. K. (2012). Idiopathic pulmonary fibrosis. Thorax 67, 742-746.
31. Hsu, S. D., Tseng, Y. T., Shrestha, S., Lin, Y. L., Khaleel, A., Chou, C. H., Chu, C. F., Huang, H. Y., Lin, C. M., Ho, S. Y., et al. (2014). miRTarBase update 2014: an information resource for experimentally validated miRNA-target interactions. Nucleic Acids Res. 42, D78-D85.
32. Iijima, S. (1991). Helical microtubules of graphitic carbon. Nature 354, 56-58.
33. Iorio, M. V., and Croce, C. M. (2012). microRNA involvement in human cancer. Carcinogenesis 33, 1126-1133.
34. Jung, M., Schaefer, A., Steiner, I., Kempkensteffen, C., Stephan, C., Erbersdobler, A., and Jung, K. (2010). Robust microRNA stability in degraded RNA preparations from human tissue and cell samples. Clin. Chem. 56, 998-1006.
35. Karaa, Z. S., Iacovoni, J. S., Bastide, A., Lacazette, E., Touriol, C., and Prats, H. (2009). The VEGF IRESes are differentially susceptible to translation inhibition by miR-16. RNA 15, 249-254.
36. Karn, T. (2013). High-throughput gene expression and mutation profiling: current methods and future perspectives. Breast Care 8, 401-406.
37. Kendall,M., and Holgate, S. (2012). Health impact and toxicological effects of nanomaterials in the lung. Respirology 17, 743-758.
38. Kim, S. W., Ramasamy, K., Bouamar, H., Lin, A. P., Jiang, D., and Aguiar, R. C. (2012). MicroRNAs miR-125a and miR-125b constitutively activate the NF-kappaB pathway by targeting the tumor necrosis factor alpha-induced protein 3 (TNFAIP3, A20). Proc. Natl Acad. Sci. U.S.A. 109, 7865-7870.
39. Kobayashi, N., Naya, M., Ema, M., Endoh, S., Maru, J., Mizuno, K., and Nakanishi, J. (2010). Biological response and morphological assessment of individually dispersed multi-wall carbon nanotubes in the lung after intratracheal instillation in rats. Toxicology 276, 143-153.
40. Lee, D. D., and Seung, H. S. (1999). Learning the parts of objects by non-negative matrix factorization. Nature 401, 788-791.
41. Lee, R. C., Feinbaum, R. L., and Ambros, V. (1993). The C. elegans heterochronic gene lin-4 encodes small RNAs with antisense complementarity to lin-14. Cell 75, 843-854.
42. Lewis, B. P., Burge, C. B., and Bartel, D. P. (2005). Conserved seed pairing, often flanked by adenosines, indicates that thousands of human genes are microRNA targets. Cell 120, 15-20.
43. Liu, L. Z., Li, C., Chen, Q., Jing, Y., Carpenter, R., Jiang, Y., Kung, H. F., Lai, L., and Jiang, B. H. (2011). MiR-21 induced angiogenesis through AKT and ERK activation and HIF-1alpha expression. PLoS One 6, e19139.
44. Mercer, R. R., Hubbs, A. F., Scabilloni, J. F., Wang, L., Battelli, L. A., Friend, S., Castranova, V., and Porter, D. W. (2011). Pulmonary fibrotic response to aspiration of multi-walled carbon nanotubes. Part. Fibre Toxicol. 8, 21.
45. Mercer, R. R., Hubbs, A. F., Scabilloni, J. F., Wang, L., Battelli, L. A., Schwegler-Berry, D., Castranova, V., and Porter, D. W. (2010). Distribution and persistence of pleural penetrations by multi-walled carbon nanotubes. Part. Fibre Toxicol. 7, 28.
46. Mercer, R. R., Scabilloni, J. F., Hubbs, A. F., Battelli, L. A., McKinney, W., Friend, S., Wolfarth, M. G., Andrew, M., Castranova, V., and Porter, D. W. (2013a). Distribution and fibrotic response following inhalation exposure to multiwalled carbon nanotubes. Part. Fibre Toxicol. 10, 33.
47. Mercer, R. R., Scabilloni, J. F., Hubbs, A. F., Wang, L., Battelli, L. A., McKinney, W., Castranova, V., and Porter, D. W. (2013b). Extrapulmonary transport of MWCNT following inhalation exposure. Part. Fibre Toxicol. 10, 38.
48. Mitchell, P. S., Parkin, R. K., Kroh, E. M., Fritz, B. R., Wyman, S. K., Pogosova-Agadjanyan, E. L., Peterson, A., Noteboom, J., O'Briant, K. C., Allen, A., et al. (2008). Circulating microRNAs as stable blood-based markers for cancer detection. Proc. Natl. Acad. Sci. U.S.A. 105, 10513-10518.
49. Mohamed, J. S., Lopez, M. A., and Boriek, A. M. (2010). Mechanical stretch up-regulates microRNA-26a and induces human airway smooth muscle hypertrophy by suppressing glycogen synthase kinase-3beta. J. Biol. Chem. 285, 29336-29347.
50. Moriyama, T., Ohuchida, K., Mizumoto, K., Yu, J., Sato, N., Nabae, T., Takahata, S., Toma, H., Nagai, E., and Tanaka, M. (2009). MicroRNA-21 modulates biological functions of pancreatic cancer cells including their proliferation, invasion, and chemoresistance. Mol. Cancer Ther. 8, 1067-1074.
51. Mraz, M., Malinova, K., Mayer, J., and Pospisilova, S. (2009). MicroRNA isolation and stability in stored RNA samples. Biochem. Biophys. Res. Commun. 390, 1-4.
52. Muller, J., Huaux, F., Moreau, N., Misson, P., Heilier, J. F., Delos, M., Arras, M., Fonseca, A., Nagy, J. B., and Lison, D. (2005). Respiratory toxicity of multi-wall carbon nanotubes. Toxicol. Appl. Pharmacol. 207, 221-231.
53. Nana-Sinkam, S. P., Hunter, M. G., Nuovo, G. J., Schmittgen, T. D., Gelinas, R., Galas, D., and Marsh, C. B. (2009). Integrating the MicroRNome into the study of lung disease. Am. J. Respir. Crit. Care Med. 179, 4-10.
54. Pacurari, M., Castranova, V., and Vallyathan, V. (2010). Singleand multi-wall carbon nanotubes versus asbestos: are the carbon nanotubes a new health risk to humans? J. Toxicol. Environ. Health Part A 73, 378-395.
55. Pacurari, M., Qian, Y., Porter, D. W., Wolfarth, M., Wan, Y., Luo, D., Ding, M., Castranova, V., Guo, N. L. (2011). Multi-walled carbon nanotube-induced gene expression in themouse lung: association with lung pathology. Toxicol Appl Pharmacol 255, 18-31.
56. Papagiannakopoulos, T., Shapiro, A., and Kosik, K. S. (2008). MicroRNA-21 targets a network of key tumor-suppressive pathways in glioblastoma cells. Cancer Res. 68, 8164-8172.
57. Peretz, A., Checkoway, H., Kaufman, J. D., Trajber, I., and Lerman, Y. (2006). Silica, silicosis, and lung cancer. Isr. Med. Assoc. J. 8, 114-118.
58. Porter, D., Sriram, K., Wolfarth, M., Jefferson, A., Schwegler-Berry, D., Andrew, M., and Castranova, V. (2008). A biocompatible mediumfor nanoparticle dispersion. Nanotoxicology 2, 144-154.
59. Porter, D. W., Hubbs, A. F., Chen, B. T., McKinney, W., Mercer, R. R., Wolfarth, M. G., Battelli, L., Wu, N., Sriram, K., Leonard, S., et al. (2013). Acute pulmonary dose-responses to inhaled multi-walled carbon nanotubes. Nanotoxicology 7, 1179-1194.
60. Porter, D. W., Hubbs, A. F., Mercer, R. R., Wu, N., Wolfarth, M. G., Sriram, K., Leonard, S., Battelli, L., Schwegler-Berry, D., Friend, S., et al. (2010). Mouse pulmonary dose-and time course-responses induced by exposure to multi-walled carbon nanotubes. Toxicology 269, 136-147.
61. Putman, R. K., Rosas, I. O., and Hunninghake, G. M. (2014). Genetics and early detection in idiopathic pulmonary fibrosis. Am. J. Respir. Crit. Care Med. 189, 770-778.
62. Rane, S., He, M., Sayed, D., Vashistha, H., Malhotra, A., Sadoshima, J., Vatner, D. E., Vatner, S. F., and Abdellatif, M. (2009). Downregulation of miR-199a derepresses hypoxia-inducible factor-1alpha and Sirtuin 1 and recapitulates hypoxia preconditioning in cardiac myocytes. Circ. Res. 104, 879-886.
63. Rogler, C. E., Levoci, L., Ader, T., Massimi, A., Tchaikovskaya, T., Norel, R., and Rogler, L. E. (2009). MicroRNA-23b cluster microRNAs regulate transforming growth factor-beta/bone morphogenetic protein signaling and liver stem cell differentiation by targeting Smads. Hepatology 50, 575-584.
64. Sayed, D., He, M., Hong, C., Gao, S., Rane, S., Yang, Z., and Abdellatif, M. (2010). MicroRNA-21 is a downstream effector of AKT that mediates its antiapoptotic effects via suppression of Fas ligand. J. Biol. Chem. 285, 20281-20290.
65. Schwartz, D. A., Helmers, R. A., Galvin, J. R., Van Fossen, D. S., Frees, K. L., Dayton, C. S., Burmeister, L. F., and Hunninghake, G. W. (1994). Determinants of survival in idiopathic pulmonary fibrosis. Am. J. Respir. Crit. Care Med. 149, 450-454.
66. Selbach, M., Schwanhausser, B., Thierfelder, N., Fang, Z., Khanin, R., and Rajewsky, N. (2008). Widespread changes in protein synthesis induced by microRNAs. Nature 455, 58-63.
67. Sessa, R., and Hata, A. (2013). Role of microRNAs in lung development and pulmonary diseases. Pulm. Circ. 3, 315-328.
68. Shen, J., Yang, X., Xie, B., Chen, Y., Swaim, M., Hackett, S. F., and Campochiaro, P. A. (2008). MicroRNAs regulate ocular neovascularization. Mol. Ther. 16, 1208-1216.
69. Shiels, M. S., Albanes, D., Virtamo, J., and Engels, E. A. (2011). Increased risk of lung cancer in men with tuberculosis in the alpha-tocopherol, beta-carotene cancer prevention study. Cancer Epidemiol. Biomarkers Prev. 20, 672-678.
70. Snyder-Talkington, B. N., Dymacek, J., Porter, D. W., Wolfarth, M. G., Mercer, R. R., Pacurari, M., Denvir, J., Castranova, V., Qian, Y., and Guo, N. L. (2013). System-based identification of toxicity pathways associated with multi-walled carbon nanotubeinduced pathological responses. Toxicol. Appl. Pharmacol. 272, 476-489.
71. Strieter, R. M. (2008). What differentiates normal lung repair and fibrosis? Inflammation, resolution of repair, and fibrosis. Proc. Am. Thorac. Soc. 5, 305-310.
72. Suarez, Y., Wang, C., Manes, T. D., and Pober, J. S. (2010). Cutting edge: TNF-induced microRNAs regulate TNF-induced expression of E-selectin and intercellular adhesion molecule-1 on human endothelial cells: feedback control of inflammation. J. Immunol. 184, 21-25.
73. Subramanian, A., Tamayo, P., Mootha, V. K., Mukherjee, S., Ebert, B. L., Gillette, M. A., Paulovich, A., Pomeroy, S. L., Golub, T. R., Lander, E. S., and Mesirov, J. P. (2005). Gene set enrichment analysis: a knowledge-based approach for interpreting genome-wide expression profiles. Proc. Natl. Acad. Sci. U.S.A. 102, 15545-15550.
74. Sugimura, K., Miyata, H., Tanaka, K., Hamano, R., Takahashi, T., Kurokawa, Y., Yamasaki, M., Nakajima, K., Takiguchi, S., Mori, M., et al. (2012). Let-7 expression is a significant determinant of response to chemotherapy through the regulation of IL-6/STAT3 pathway in esophageal squamous cell carcinoma. Clin. Cancer Res. 18, 5144-5153.
75. Terao, M., Fratelli, M., Kurosaki, M., Zanetti, A., Guarnaccia, V., Paroni, G., Tsykin, A., Lupi, M., Gianni, M., Goodall, G. J., et al. (2011). Induction of miR-21 by retinoic acid in estrogen receptor-positive breast carcinoma cells: biological correlates andmolecular targets. J. Biol. Chem. 286, 4027-4042.
76. Tili, E., Michaille, J. J., Cimino, A., Costinean, S., Dumitru, C. D., Adair, B., Fabbri, M., Alder, H., Liu, C. G., Calin, G. A., et al. (2007). Modulation of miR-155 and miR-125b levels following lipopolysaccharide/TNF-alpha stimulation and their possible roles in regulating the response to endotoxin shock. J. Immunol. 179, 5082-5089.
77. Tsukamoto, Y., Nakada, C., Noguchi, T., Tanigawa, M., Nguyen, L. T., Uchida, T., Hijiya, N., Matsuura, K., Fujioka, T., Seto, M., et al. (2010). MicroRNA-375 is downregulated in gastric carcinomas and regulates cell survival by targeting PDK1 and 14-3-3zeta. Cancer Res. 70, 2339-2349.
78. Walter, N., Collard, H. R., and King, T. E., Jr. (2006). Current perspectives on the treatment of idiopathic pulmonary fibrosis. Proc. Am. Thorac. Soc. 3, 330-338.
79. Wu, H., Zhu, S., and Mo, Y. Y. (2009). Suppression of cell growth and invasion by miR-205 in breast cancer. Cell Res. 19, 439-448.
80. Xi, Y., Nakajima, G., Gavin, E., Morris, C. G., Kudo, K., Hayashi, K., and Ju, J. (2007). Systematic analysis of microRNA expression of RNA extracted from fresh frozen and formalin-fixed paraffin-embedded samples. RNA 13, 1668-1674.
81. Xiao, F., Zuo, Z., Cai, G., Kang, S., Gao, X., and Li, T. (2009). miRecords: an integrated resource for microRNA-target interactions. Nucleic Acids Res. 37, D105-D110.
82. Xu, N., Zhang, L., Meisgen, F., Harada, M., Heilborn, J., Homey, B., Grander, D., Stahle, M., Sonkoly, E., and Pivarcsi, A. (2012). MicroRNA-125b down-regulates matrix metallopeptidase 13 and inhibits cutaneous squamous cell carcinoma cell proliferation, migration, and invasion. J. Biol. Chem. 287, 29899-29908.
83. Yang, X., Liang, L., Zhang, X. F., Jia, H. L., Qin, Y., Zhu, X. C., Gao, X. M., Qiao, P., Zheng, Y., Sheng, Y. Y., et al. (2013). MicroRNA-26a suppresses tumor growth and metastasis of human hepatocellular carcinoma by targeting interleukin-6-Stat3 pathway. Hepatology 58, 158-170.
84. Ye, W., Lv, Q., Wong, C. K., Hu, S., Fu, C., Hua, Z., Cai, G., Li, G., Yang, B. B., and Zhang, Y. (2008). The effect of central loops in miRNA:MRE duplexes on the efficiency of miRNA-mediated gene regulation. PLoS One 3, e1719.
85. Yu, Y. Y., Pinsky, P. F., Caporaso, N. E., Chatterjee, N., Baumgarten, M., Langenberg, P., Furuno, J. P., Lan, Q., and Engels, E. A. (2008). Lung cancer risk following detection of pulmonary scarring by chest radiography in the prostate, lung, colorectal, and ovarian cancer screening trial. Arch. Int. Med. 168, 2326-2332; discussion 2332.
86. Zhang, X., Daucher, M., Armistead, D., Russell, R., and Kottilil, S. (2013). MicroRNA expression profiling in HCV-infected human hepatoma cells identifies potential anti-viral targets induced by interferon-alpha. PLoS One 8, e55733.
87. Zhang, X., Ng, W. L., Wang, P., Tian, L., Werner, E., Wang, H., Doetsch, P., and Wang, Y. (2012a). MicroRNA-21 modulates the levels of reactive oxygen species by targeting SOD3 and TNFalpha. Cancer Res. 72, 4707-4713.
88. Zhang, Y., Fan, K. J., Sun, Q., Chen, A. Z., Shen, W. L., Zhao, Z. H., Zheng, X. F., and Yang, X. (2012b). Functional screening for miRNAs targeting Smad4 identified miR-199a as a negative regulator of TGF-beta signalling pathway. Nucleic Acids Res. 40, 9286-9297.
89. Zhou, X., Ren, Y., Moore, L., Mei, M., You, Y., Xu, P., Wang, B., Wang, G., Jia, Z., Pu, P., et al. (2010). Downregulation of miR-21 inhibits EGFR pathway and suppresses the growth of human glioblastoma cells independent of PTEN status. Lab. Invest. 90, 144-155.
90. Zhu, N., Zhang, D., Xie, H., Zhou, Z., Chen, H., Hu, T., Bai, Y., Shen, Y., Yuan, W., Jing, Q., and Qin, Y. (2011). Endothelialspecific intron-derived miR-126 is down-regulated in human breast cancer and targets both VEGFA and PIK3R2. Mol. Cell. Biochem. 351, 157-164.