Читать книгу Genomic and Epigenomic Biomarkers of Toxicology and Disease - Группа авторов - Страница 67

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 these miRNAs were located in abnormal chromosomal positions of MM patients and that their target genes, such as CDKN2A, NF2, JUN, HGF, and PDGFA, were most likely to affect the occurrence and development of MM. This pioneering research has opened up a new kind of approach in the field. Since its publication in 2009, more studies have discussed the role of miRNA in MM in detail (Truini et al. 2014).