**2. Synthesis/biogenesis of miRNA**

Synthesis of miRNA takes place in the nucleus as well as in the cytoplasm. Genes encoding miRNAs are present in the form of a cluster and contain introns (**Figure 1**). These genes are transcribed by polymerase II with the generation of the primary precursor pri-miRNA. This precursor miRNA consists of a 3<sup>0</sup> poly-A tail and a 5<sup>0</sup> end cap [19, 20] with a stem-loop structure. RNase 3 Drosha cleaves this structure with the help of its Pasha cofactor DGCR8. This resultant cleaved, precursor structure is known as pre-miRNA and consists of �70–90 nucleotides [21]. This �70 nt precursor is exported to the cytoplasm by Exportin-5.

In the cytoplasm, the whole pri-miRNA is recruited by a RNA-induced silencing complex (RISC) and is converted into mature miRNA. These are mediated by an RISC leaching complex (RLS), which is basically a multiprotein complex and consists of a double-stranded RNA domain protein (DICER), tar RNA-binding protein (TARB), and the Ago 2 protein. The RNAse 3 DICER along with its cofactor yields duplex miRNA (19–25 nucleotide duplex miRNA with 2 nucleotide overhangs at each 3<sup>0</sup> end). During the process of cleavage, two strands are formed, namely, a functional and a passenger strand. The functional strand along with the Ago protein (RISC) is involved in gene silencing function, while the passenger strand is degraded due to its instability. This miRISC incorporates one strand of miRNA (functional strand and guide strand) so that it takes the guidance from this complex to target mRNA (complementary) for its degradation or inhibition at the translational level [22]. miRNA is processed in the cytosol and transported to the blood. It is resistant to degradation because it is carried by complexes of lipoprotein inclusions [23] or in the form of exosomes [24, 25].

**4. Diagnosis of cancer**

**Figure 2.**

**Figure 3.**

*Mechanism of miRNA.*

*Mechanism of action of miRNA.*

*MicroRNA: A Signature for Cancer Diagnostics DOI: http://dx.doi.org/10.5772/intechopen.90063*

**5.1 Breast cancer**

**5**

There are reported differences in the expression pattern of miRNA in normal

downregulated in different kinds of cancers [28]. Due to its small size and resistance to RNase-mediated degradation, they have the potential as powerful biomarkers for cancer diagnosis [29]. miRNA expression is involved with the rearrangement of chromosomes, methylation of the promoter region, and transcriptional regulation. miRNA-mediated aberrations in one or more of these processes can culminate in

and cancer cells [27]. Some miRNAs are overexpressed, while the others are

alterations in protein and mRNA expression [30].

**5. Types of miRNA and cancer according to organs**

Different miRNAs are involved in different types of cancers:

Breast cancer is the most prevalent form of cancer in women. Among 12.7 million cancer cases globally, breast cancer is most frequently diagnosed, that is, 23 and 14% deaths due to breast cancer have been reported [1, 31]. The alarmingly increasing mortality data coupled with increases in relapses warrants an improved molecular understanding of the etiology and mechanistic details that contribute to the chemoresistance. There are four subtypes (intrinsic) of breast cancer. These are ErbB2<sup>+</sup> (epidermal growth factor receptor 2-positive (also called HER2)), luminal A

**Figure 1.** *Biogenesis of microRNA.*
