Genomic and Epigenomic Biomarkers of Toxicology and Disease - Группа авторов

Скачать книгу

assessment. Recently, using EV-associated miRNAs or circulating free miRNAs in serum as biomarkers has made it possible to diagnose thirteen types of cancer with an accuracy of 90% or more (Ogata-Kawata et al. 2014; Shimomura et al. 2016; Yokoi et al. 2018; Yao et al. 2019; Asano et al. 2019; Shiino et al. 2019; Usuba et al. 2019; Asakura et al. 2020). The development of next-generation toxicity tests using miRNA as a biomarker is therefore expected.

      Our studies identified forty-two novel miRNAs—such as miR-122 and miR-192—as candidate liver damage biomarkers. Using these novel biomarkers, it may be possible to elucidate the mechanism of hepatotoxicity caused by the administration of drugs or chemical substances other than carbon tetrachloride. Since EVs in blood are secreted by a wide variety of cells, it is necessary to clarify the origin of the EV-associated miRNAs. In addition to their utility as markers of hepatotoxicity, EV-associated miRNAs are expected to be valuable as biomarkers of toxicity that targets other organs, such as the kidney, the lung, and the heart.

      Although this study analyzed the effects of carbon tetrachloride administration at a single time point, twenty-four hours, evaluating the time courses of biomarkers in response to the repeated administration of carbon tetrachloride may be applicable if we want to shorten chronic toxicity tests and long-term carcinogenicity tests.

      It may also be important to elucidate the function of the identified EV-associated miRNAs induced by hepatotoxicity in vivo.

      Acknowledgments

      The authors thank N. Moriyama, T. Momiyama, E. Tachihara, M. Uchiyama, and H. Aihara for excellent technical assistance. The images of mice, cows and cultured cells are from TogoTV (©2016 DBCLS TogoTV/CC-BY-4.0).

      The authors declare no competing interests.

      Funding

      This work was supported in part by Research on the Regulatory Science of Pharmaceuticals and Medical Devices (20mk0101163j0202), Research on the Development of New Drugs (20ak0101093j003) from the Japan Agency for Medical Research and Development, the Health Sciences Research Grants from the Ministry of Health, Labor, and Welfare, Japan, (H30-KAGAKU-IPPAN-002, 21KD1001), and JSPS KAKENHI (18K19315) to R.O.; Grant-in-Aid from the Research Program on Hepatitis from Japan Agency for Medical Research and Development (AMED: 16fk0310512h0005, 17fk0310101h0001 and 18fk0310101h0002) and Grants-in -Aid from a Project for Cancer research and Therapeutic Evolution (P-CREATE) to T. O.; JSPS KAKENHI (18K07053) to Y. H.

      References

      1 Alberti, C. and Cochella, L. (2017). A framework for understanding the roles of miRNAs in animal development. Development 144: 2548–2559.

      2 Ambros, V. (2004). The functions of animal microRNAs. Nature 431: 350–355.

      3 Asakura, K., Kadota, T., Matsuzaki, J., Yoshida, Y., Yamamoto, Y., Nakagawa, K., Takizawa, S., Aoki, Y., Nakamura, E., Miura, J., Sakamoto, H., Kato, K., Watanabe, S.I., and Ochiya, T. (2020). A miRNA-based diagnostic model predicts resectable lung cancer in humans with high accuracy. Commun. Biol. 3: 134.

      4 Asano, N., Matsuzaki, J., Ichikawa, M., Kawauchi, J., Takizawa, S., Aoki, Y., Sakamoto, H., Yoshida, A., Kobayashi, E., Tanzawa, Y., Nakayama, R., Morioka, H., Matsumoto, M., Nakamura, M., Kondo, T., Kato, K., Tsuchiya, N., Kawai, A., and Ochiya, T. (2019). A serum microRNA classifier for the diagnosis of sarcomas of various histological subtypes. Nat. Commun. 10: 1299.

      5 Baek, R., Varming, K., and Jorgensen, M.M. (2016). Does smoking, age or gender affect the protein phenotype of extracellular vesicles in plasma? Transfus. Apher. Sci. 55: 44–52.

      6 Bala, S., Petrasek, J., Mundkur, S., Catalano, D., Levin, I., Ward, J., Alao, H., Kodys, K., and Szabo, G. (2012). Circulating microRNAs in exosomes indicate hepatocyte injury and inflammation in alcoholic, drug-induced, and inflammatory liver diseases. Hepatology 56: 1946–1957.

      7 Baran, J., Baj-Krzyworzeka, M., Weglarczyk, K., Szatanek, R., Zembala, M., Barbasz, J., Czupryna, A., Szczepanik, A., and Zembala, M. (2010). Circulating tumour-derived microvesicles in plasma of gastric cancer patients. Cancer Immunol. Immunother. 59: 841–850.

      8 Birbrair, A., Zhang, T., Wang, Z.M., Messi, M.L., Mintz, A., and Delbono, O. (2015). Pericytes at the intersection between tissue regeneration and pathology. Clin. Sci. (Lond) 128: 81–93.

      9 Birbrair, A., Zhang, T., Wang, Z.M., Messi, M.L., Olson, J.D., Mintz, A., and Delbono, O. (2014). Type-2 pericytes participate in normal and tumoral angiogenesis. Am. J. Physiol. Cell. Physiol. 307: C25–38.

      10 Bohnsack, M.T., Czaplinski, K., and Gorlich, D. (2004). Exportin 5 is a RanGTP-dependent dsRNA-binding protein that mediates nuclear export of pre-miRNAs. RNA 10: 185–191.

      11 Borchert, G.M., Lanier, W., and Davidson, B.L. (2006). RNA polymerase III transcribes human microRNAs. Nat. Struct. Mol. Biol. 13: 1097–1101.

      12 Bray, F., Ferlay, J., Soerjomataram, I., Siegel, R.L., Torre, L.A., and Jemal, A. (2018). Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J. Clin. 68: 394–424.

      13 Carmeliet, P. and Jain, R.K. (2000). Angiogenesis in cancer and other diseases. Nature 407: 249–257.

      14 Cazzoli, R., Buttitta, F., Di Nicola, M., Malatesta, S., Marchetti, A., Rom, W.N., and Pass, H.I. (2013). microRNAs derived from circulating exosomes as noninvasive biomarkers for screening and diagnosing lung cancer. J. Thorac. Oncol. 8: 1156–1162.

      15 Chan, Y.K., Zhang, H., Liu, P., Tsao, S.W., Lung, M.L., Mak, N.K., Ngok-Shun Wong, R., and Ying-Kit Yue, P. (2015). Proteomic analysis of exosomes from nasopharyngeal carcinoma cell identifies intercellular transfer of angiogenic proteins. Int. J. Cancer 137: 1830–1841.

      16 Chen, L. and Han, X. (2015). Anti-PD-1/PD-L1 therapy of human cancer: Past, present, and future. J. Clin. Invest. 125: 3384–3391.

      17 Chendrimada, T.P., Gregory, R.I., Kumaraswamy, E., Norman, J., Cooch, N., Nishikura, K., and Shiekhattar, R. (2005). TRBP recruits the Dicer complex to Ago2 for microRNA processing and gene silencing. Nature 436: 740–744.

      18 Cho, Y.E., Kim, S.H., Lee, B.H., and Baek, M.C. (2017). Circulating plasma and exosomal microRNAs as indicators of drug-induced organ injury in rodent models. Biomol. Ther. (Seoul) 25: 367–373.

      19 Choi, D.S., Park, J.O., Jang, S.C., Yoon, Y.J., Jung, J.W., Choi, D.Y., Kim, J.W., Kang, J.S., Park, J., Hwang, D., Lee, K.H., Park, S.H., Kim, Y.K., Desiderio, D.M., Kim, K.P., and Gho, Y.S. (2011). Proteomic analysis of microvesicles derived from human colorectal cancer ascites. Proteomics 11: 2745–2751.

      20 Chopra, P., Roy, S., Ramalingaswami, V., and Nayak, N.C. (1972). Mechanism of carbon tetrachloride hepatotoxicity. An in vivo study of its molecular basis in rats and monkeys. Lab. Invest. 26: 716–727.

      21 Clark, D.J., Fondrie, W.E., Yang, A., and Mao, L. (2016). Triple SILAC quantitative proteomic analysis reveals differential abundance of cell signaling proteins between normal and lung cancer-derived exosomes. J. Proteomics 133: 161–169.

      22 Colombo, M., Raposo, G., and Thery, C. (2014). Biogenesis, secretion, and intercellular interactions of exosomes and other extracellular vesicles. Annu. Rev. Cell. Dev. Biol. 30: 255–289.

      23 Conde-Vancells, J., Rodriguez-Suarez, E., Embade, N., Gil, D., Matthiesen, R., Valle, M., Elortza, F., Lu, S.C., Mato, J.M., and Falcon-Perez, J.M. (2008). Characterization and comprehensive proteome profiling of exosomes secreted by hepatocytes. J. Proteome. Res. 7: 5157–5166.

      24 Coufal, N.G., Garcia-Perez, J.L., Peng, G.E., Yeo, G.W., Mu, Y., Lovci, M.T., Morell, M., O’Shea, K.S., Moran, J.V., and Gage, F.H. (2009). L1 retrotransposition in human neural progenitor cells. Nature 460: 1127–1131.

      25 Cufaro, M.C., Pieragostino, D., Lanuti, P., Rossi, C., Cicalini, I., Federici, L., De Laurenzi, V., and Del Boccio, P. (2019). Extracellular vesicles and their potential use in monitoring cancer progression and therapy: The contribution of proteomics. J. Oncol. 2019: 1639854.

      26 De

Скачать книгу