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miRNAs are small non-coding RNAs with about 22 nucleotides of length that seems to regulate major parts of human genes when combined with the RNA-induced silencing complex. When this happens, miRNAs control gene regulation by degradation of the mRNA through cleavage or by blocking protein synthesis.
It is estimated that miRNAs can target 33% of human genes, attesting to their importance in gene regulation. Most cellular processes, from differentiation, proliferation to apoptosis, can be regulated by miRNAs. Besides, miRNAs are involved in disease processes. Changes in miRNA gene expression are closely related to the development and progression of malignancies and other diseases. In recent years, a large number of studies showed that miRNAs profiling had an important role as disease biomarkers, as a powerful tool to understand gene regulation mechanisms such as development mechanisms and gene regulatory networks.
Figure 1. The biogenesis and mechanism of miRNA. (McGuire A, et al., 2015)
To improve the survival rate of cancer patients, highly specific and more sensitive biomarkers should be discovered and developed for tumor screening and early detection, as well as for survival prediction by monitoring the response to chemotherapeutic drugs. Thus, miRNAs as biomarkers provide great tools to evaluate cancer development. They play an important role in almost all cellular pathways governing human malignancies, such as cancer progression, cell invasion and metastasis, cell survival, and response to therapeutic drugs. Besides, miRNAs also act as oncogenes and tumor-suppressor genes; therefore, they have great potential to serve as promising biomarkers for cancer.
Recent advances in the field of miRNA suggest that genetic variation or polymorphisms present in the miRNA pathway are related to the prognosis/progression of diseases and drug responses, which are powerful tools to study the biology of diseases. A polymorphism of mature miRNAs may affect the expression of multiple genes and have serious consequences, whereas a polymorphism of miRNA target site may be more target and/or pathway specific. In a follow-up report, miR-24 was confirmed to act as a p53-independent tumor suppressor miRNA, and loss of mir-24 function due to the miRSNPs not only confers drug resistance but also imparts a growth advantage to immortalized cells and induces tumor transformation. Therefore, recent advances in the miRNA field have resulted in the understanding of entirely new mechanisms of cellular transformation and drug-resistance caused by loss of miRNA function by miRNA variants (miRSNP/miR-polymorphisms). Furthermore, the discovery of the role of miRNA in drug resistance and miR-polymorphisms to predict drug response has led to the development of a new field in biomedical science, called miRNA pharmacogenomics, which studies the effect of miRNA and miR-polymorphisms on the expression of drug target genes, predicts drug behavior and improves drug efficacy. Detection of miRNA-polymorphisms may improve diagnosis, treatment and prognosis in patients and has far-reaching significance in the fields of pharmacogenomics and precision medicine.
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