**5. miRNA and its expression in breast cancer**

It is well known that in most of the cancer cells studied so far the expression of miRNA has generally decreased. This is not surprising, for miRNAs generally act as tumor suppressors in most cells. Moreover, lower levels of miRNA are found in tumor cells that are poorly differentiated in contrast to those with a higher degree of differentiation. This fundamental finding suggests that global changes in the expression levels of miRNA are intimately associated with the degree of differentiation of aberrant cells. It has been demonstrated recently that a number of miRNAs are expressed at lower levels in tumor-derived cell lines than in the corresponding human tissue. Another study has shown that down-regulation of the expression of miRNA levels in cancer cells resulted in tumorigenesis and that the knockout of Dicer and Drosha, molecules necessary for miRNA biogenesis, led to the complete loss of expression of miRNA. Finally, accelerated growth with enhanced invasive properties occurred when tumor cells were injected into nude mice, strongly suggesting that the loss of miRNA expression leads to enhanced tumorigenesis [7].

Several studies have tackled miRNA profiling and their results indicate that many miRNAs are overexpressed in breast cancer. Although several functions of miRNAs have been investigated, it has become clear that many types of experiment will be required to establish whether miRNAs can be used as novel therapeutic agents or as diagnostic markers. One fact is clear:

**Figure 1.** Hierarchical clustering view of the normalized expression levels of miRNA measured in plasma and corresponding miRNA precursor levels in tissue obtained from TCGA RNA-seq data.

tumor metastasis may be promoted through the enhanced expression of pro-oncogenic/prometastatic miRNAs or via the down-regulation of anti-oncogenic/anti-metastatic miRNAs. A number of miRNAs have been shown to be deregulated in breast cancer, indicating that particular miRNAs may be involved in the modulation of oncogenesis [3, 15]. miR-10b, miR-125b and miR-145 have been shown to be down-regulated, while miR-21 and miR-155 were upregulated, strongly suggesting that these miRNAs play important roles as tumor suppressor genes or contribute to creating an oncogene supportive environment [16]. Recently it has been demonstrated that miR-19a, miR-19b, miR-210, miR-15a, miR-16 and miR-7 are overexpressed in plasma as well as in TNBC tissue (**Figure 1**) [3]. At present, a number of research studies have reported on the oncogenic role of miR-19a/b in TNBC tumor development, which occurs due to the repression of PTEN and activation of NF-kB [3, 17]. In addition, the circulating levels of miR-19 have been associated with the efficacy of the epirubicin + paclitaxel chemotherapy regimen in Stage II and III patients with luminal A breast tumors [3, 18]. In a Japanese TNBC patient cohort study, it was reported that a high hsa-miR-210 expression level was an independent risk factor for poor prognosis [3, 19].
