**5. Concluding remarks and limitations**

By the discovery of miRNAs, a significant number of studies have been conducted to indicate the utility of miRNAs. According to the highlighted studies, miRNAs in body fluids have potential to be predictive, diagnostic or prognostic biomarkers; and also they can be therapeutic targets due to their inducer ability on tumorigenesis. Basically, miRNAs offer promising practice for screening, diagnosis, prognosis, and treatment of cancer. Therefore, these noncoding RNA fragments may be used alone or combined with other protocols to screen, diagnose, prognose, and treat cancer. However, their clinical importance is still not conclusive, and validation studies are needed for routine-based clinical application.

Evidences showed that inhibition of oncomiRs or replacement of tumor suppressive miRNAs could be used to develop innovative treatment approaches. Further studies are needed to reveal the molecular mechanisms on the regulation of miRNA biogenesis. Determination of miRNA target genes, molecular interactions between target mRNA and miRNAs, and signaling pathways will help to interpret molecular mechanisms of cancer. Besides investigations on miRNA expression patterns and

their molecular mechanisms, studies on technological developments for reliable and cost-effective miRNA applications are also extremely important to enhance minimally invasive routine miRNA applications. Methodological variability among different clinical centers is the biggest limitation for the successful combination of miRNAs in cancer management. Standardization and normalization of essential steps of miRNA applications, such as miRNA extraction, processing, biobanking, and quantitation, eliminate the clinical facility-based variations. Using internal controls and enrollment of the laboratory accreditation/validation programs may present benefits for standardization. miRNAs have potential to be therapeutic targets and treatment options. But determination of mRNAs and miRNAs interactions and obtaining the large population-based multicenter cohorts are essential to use miRNAs in therapy. Especially before the implementation of miRNAs in clinics, evaluation of miRNA panels on large patient cohorts must be achieved.
