120 Tokar, E.J., Boyd, W.A., Freedman, J.H., and Waalkes, M.P. (2013). Toxic effects of metals. In Casarett and Doull’s Toxicology: The Basic Science of Poisons, (8th edn.), edited by C. D. Klaassen. New York: McGraw Hill.
121 Tsuji, J.S., Chang, E.T., Gentry, P.R., Clewell, H.J., Boffetta, P., and Cohen, S.M. (2019). Dose-response for assessing the cancer risk of inorganic arsenic in drinking water: The scientific basis for use of a threshold approach. Crit. Rev. Toxicol. 49: 36–84.
122 USEPA. (1998). Toxicological Review of Hexavalent Chromium: Cas. No. 18540-29-9. Washington, DC: US Environmental Protection Agency.
123 Vasudevan, S., Tong, Y., and Steitz, J.A. (2007). Switching from repression to activation: MicroRNAs can up-regulate translation. Science 318: 1931–1934.
124 Wah Chu, K. and Chow, K.L. (2002). Synergistic toxicity of multiple heavy metals is revealed by a biological assay using a nematode and its transgenic derivative. Aquat. Toxicol. 61: 53–64.
125 Wang, L., Qiu, J.G., He, J., Liu, W.J., Ge, X., Zhou, F.M., Huang, Y.X., Jiang, B.H., and Liu, L.Z. (2019). Suppression of miR-143 contributes to overexpression of IL-6, HIF-1alpha and NF-kappaB p65 in Cr(VI)-induced human exposure and tumor growth. Toxicol. Appl. Pharmacol. 378: 114603.
126 Wang, Y., Su, H., Gu, Y., Song, X., and Zhao, J. (2017). Carcinogenicity of chromium and chemoprevention: A brief update. Onco. Targets Ther. 10: 4065–4079.
127 Weber, J.A., Baxter, D.H., Zhang, S., Huang, D.Y., Huang, K.H., Lee, M.J., Galas, D.J., and Wang, K. (2010). The microRNA spectrum in 12 body fluids. Clin. Chem. 56: 1733–1741.
128 WHO. (1993). Evaluation of certain food additives and contaminants: Forty-first report of the Joint FAO/WHO Expert Committee on Food Additives. World Health Organ. Tech. Rep. Ser. 837: 1–53.
129 WHO. (2018). Arsenic [Online]. https://www.who.int/news-room/fact-sheets/detail/arsenic (accessed May 30 2021).
130 Wimmer, I., Troscher, A.R., Brunner, F., Rubino, S.J., Bien, C.G., Weiner, H.L., Lassmann, H., and Bauer, J. (2018). Systematic evaluation of RNA quality, microarray data reliability and pathway analysis in fresh, fresh frozen and formalin-fixed paraffin-embedded tissue samples. Sci. Rep. 8: 6351.
131 Wise, J.P., Sr., Wise, S.S., and Little, J.E. (2002). The cytotoxicity and genotoxicity of particulate and soluble hexavalent chromium in human lung cells. Mutat. Res. 517: 221–229.
132 Xu, M., Yu, Z., Hu, F., Zhang, H., Zhong, L., Han, L., An, Y., Zhu, B., and Zhang, H. (2017). Identification of differential plasma miRNA profiles in Chinese workers with occupational lead exposure. Biosci. Rep. 37.
133 Xu, Y., Zou, Z., Liu, Y., Wang, Q., Sun, B., Zeng, Q., Liu, Q., and Zhang, A. (2020). miR-191 is involved in renal dysfunction in arsenic-exposed populations by regulating inflammatory response caused by arsenic from burning arsenic-contaminated coal. Hum Exp Toxicol 39: 37–46.
134 Yang, L., Zhang, Y., Wang, F., Luo, Z., Guo, S., and Strahle, U. (2020). Toxicity of mercury: Molecular evidence. Chemosphere 245: 125586.
135 Young, J.L., Yan, X., Xu, J., Yin, X., Zhang, X., Arteel, G.E., Barnes, G.N., States, J.C., Watson, W.H., Kong, M., Cai, L., and Freedman, J.H. (2019). Cadmium and high-fat diet disrupt renal, cardiac and hepatic essential metals. Sci. Rep. 9: 14675.
136 Yuan, W., Liu, L., Liang, L., Huang, K., Deng, Y., Dong, M., Chen, J., Wang, G., and Zou, F. (2020). MiR-122-5p and miR-326-3p: Potential novel biomarkers for early detection of cadmium exposure. Gene 724: 144156.
137 Zampetaki, A., Albrecht, A., and Steinhofel, K. (2018). Long non-coding RNA structure and function: Is there a link? Front Physiol. 9: 1201.
138 Zeng, Q., Zou, Z., Wang, Q., Sun, B., Liu, Y., Liang, B., Liu, Q., and Zhang, A. (2019). Association and risk of five miRNAs with arsenic-induced multiorgan damage. Sci. Total Environ. 680: 1–9.
139 Zenobia, C. and Hajishengallis, G. (2015). Basic biology and role of interleukin-17 in immunity and inflammation. Periodontol 2000, 69: 142–159.
140 Zhang, L., Gao, Y., Wu, S., Zhang, S., Smith, K.R., Yao, X., and Gao, H. (2020). Global impact of atmospheric arsenic on health risk: 2005 to 2015. Proc. Natl. Acad. Sci. USA 117: 13975–13982.
141 Zheng, L., Jiang, Y.L., Fei, J., Cao, P., Zhang, C., Xie, G.F., Wang, L.X., Cao, W., Fu, L., and Zhao, H. (2021). Circulatory cadmium positively correlates with epithelial-mesenchymal transition in patients with chronic obstructive pulmonary disease. Ecotoxicol. Environ. Saf. 215: 112164.
142 Zhou, Q. and Xi, S. (2018). A review on arsenic carcinogenesis: Epidemiology, metabolism, genotoxicity and epigenetic changes. Regul. Toxicol. Pharmacol. 99: 78–88.
5 MicroRNA Biomarkers of Malignant Mesothelioma
Lijin Zhu, Fangfang Zhang, Min Zhang, Hailing Xia, Xiuyuan Yuan, and Yanan Gao
Hangzhou Medical College
Pleural malignant mesothelioma (MM), which arises from the cells that line the lung and the chest cavity (pleura), is a highly aggressive tumor with a high recurrence rate after surgical resection, and is insensitive to chemotherapy and radiotherapy. The median survival time commonly does not exceed 12–18 months after diagnosis (Wright et al. 2013). Therefore biomarkers for early detection are imperative even for experienced pathologists (Wu et al. 2013; Zhang et al. 2014). Approximately 80% of the cases of pleural MM are attributed to asbestos exposure, and the latency after exposure could be 20–60 years (Rascoe et al. 2012). Asbestos exposure, a genetic basis, and other factors are likely to contribute to the etiology of pleural MM (Robinson and Lake 2005).
MicroRNA (miRNA) is a kind of highly conserved, non-coding, single-stranded small RNA with a length of 18–25 nucleotides (Kirschner et al. 2011). About 35,828 mature miRNAs have been found in human genome, which can be divided into 223 species; these miRNAs regulate one third of human genes. The same miRNA can regulate single or multiple target genes and, in turn, the same gene can be regulated by multiple miRNAs (Luo et al. 2010) . Here mature miRNAs bind to untranslated sequences at the 3ʹ-end of the target mRNA through base complementary pairing, to inhibit mRNA translation or degradation, thereby regulating gene expression and playing a role in promoting or inhibiting cancer.
During the two decades since Calin et al. (2002) first discovered two miRNAs (miR-15 and miR-16) closely related to the occurrence of chronic lymphoblastic leukemia, miRNAs have been proved to play a key role in cancer progression, treatment response, and diagnosis (Berindan-Neagoe et al. 2014; Hata and Lieberman 2015). The tumor-promoting or tumor-suppressing effects of miRNAs in various cancers depend on their expression levels. More and more researchers have applied miRNAs to the diagnosis and treatment of malignant tumors—for example the miR-200 family, miR-9, miR-34, miR-21, and miR-340 in the prognosis of pancreatic cancer (Zöller 2013) and miR-140 and miR-145 in the diagnosis and treatment of ovarian cancer (Banno et al., 2014).
The earliest study on miRNA in relation to MM began with Guled’s research in 2009 (Guled et al. 2009). In this study, the miRNA expression profiles of seventeen freshly frozen MM tissue samples and normal pericardium were analyzed using miRNA microarray, and multiple differentially expressed miRNAs between MM tissues and adjacent tissues were found. Moreover, different tissue subtypes of MM expressed specific miRNAs: for example, epithelial MM expressed miR-135b, miR-181a-2*, miR-499-5p, miR-517b, miR-519d, miR-615-5p, and miR-624, biphasic MM expressed miR-218-2*, miR-346, miR-377*, miR-485-5p, and miR-525-3p, and sarcomatous MM expressed miR-301b, miR-433, and miR-543. In this study, patients’ exposure to smoking and asbestos were also considered, and some miRNAs were specifically expressed in smoking patients (miR-379, miR-301a, miR-299-3p, miR-455-3p, and miR-127-3p); No miRNAs specifically expressed in asbestos exposure samples were found, but this absence may be related to different methods of asbestos exposure assessment. Other study found that most of