## 4 Discussion  
MiRNAs are small non-coding RNA molecules that are involved in the regulation of cancer development as oncomirs or tumor suppressors. Furthermore, they are considered to be good candidates for cancer diagnostics [4]. However, more than 2500 miRNAs have been identified to this date that makes searching for promising biomarker candidates difficult. Most of the studies focus on miRNA expression in body fluids or cell cultures exclusively. Here, we made a comprehensive study about the cell-free expression of three well-known miRNAs in cell cultures and plasma samples. MiR-205 is proved to be a tumor suppressor that plays pivotal role in the regulation of cell proliferation and invasiveness of cancer and considered to be a promising therapeutic target [15; 16]. The pivotal role of miR-205 in cancer is strongly suggested by our bioinformatic analysis that revealed several processes related to cancer. It is further supported by previous studies where the expression of miR-205 was confirmed to be altered in breast, endometrial, prostate, lung, bladder, thyroid, and colorectal cancer [16; 17; 18; 19; 20; 21; 22; 23]. The relatively high basal expression of miR-205 in ovarian cell lines suggests its high biological relevance in ovarian tumors. It is in good agreement with the observation that the expression of miR-205 was up-regulated in ovarian tumor tissues compared to normal ovarian cells [24; 25; 26; 27; 28]. Furthermore, the cell-free expression of miR-205 proved to be high in ovarian cancer cell lines, as well as in the plasma samples of patients with ovarian cancer that was also described previously [28; 29]. To the best of our knowledge, it is the first study that analyze miR-205 expression in a Central-European population. Our pilot study strengthens the notion that miR-205 might be a promising biomarker candidate in ovarian cancer that should be further analyzed in larger sample size. \begin{table}
\begin{tabular}{c c c c c c} \hline \hline
**let/f** & & & & **miR205** & \\ \hline \multicolumn{6}{c}{**GAD DISEASE**} \\ \hline Category & Count & \(p\)-value & Category & Count & \(p\)-value \\ \hline prostate cancer ES: 2.59 & 5 & 6.25 \(\times\) 10\({}^{-4}\) & prostate cancer ES: 2.94 & 6 & 0.011 \\ ovarian cancer ES: 2.59 & 4 & 0.003 & breast cancer ES: 2.37 & 10 & 6.72 \(\times\) 10\({}^{-6}\) \\ epithelial ovarian cancer ES: 2.59 & 3 & 0.008 & endometrial cancer ES: 1.91 & 4 & 2.36 \(\times\) 10\({}^{-4}\) \\ esophageal adenocarcinoma ES: 1.41 & 3 & 0.034 & esophageal adenocarcinoma ES: 1.91 & 7 & 3.14 \(\times\) 10\({}^{-4}\) \\  & & & epithelial ovarian cancer ES: 1.91 & 5 & 0.001 \\  & & & lung cancer ES: 1.91 & 7 & 0.002 \\  & & & leukemia ES: 1.91 & 3 & 0.005 \\  & & & colorectal CancerES: 1.91 & 5 & 0.026 \\ \hline \multicolumn{6}{c}{**GOTERM Biological process**} \\ \hline Category & Count & \(p\)-value & Category & Count & \(p\)-value \\ \hline GO:0000715 nucleotide-excision repair, DNA & 3 & 1.62 \(\times\) 10\({}^{-4}\) & GO:0008285 negative regulation of cell & 9 & 1.51 \(\times\) 10\({}^{-6}\) \\ damage recognitionES: 3.98 & & & & GO:0043066 negative regulation of apoptotic & 6 & 0.002 \\  & & & & GO:0042127 regulation of cell proliferationES: & 4 & 0.007 \\  & & & & GO:0008284 positive regulation of cell & 6 & 0.003 \\  & & & & proliferationES: 1.91 & 6 & 0.003 \\  & & & & GO:0030336 negative regulation of cell & 3 & 0.002 \\  & & & migrationES: 1.76 & 3 & 0.002 \\ \hline \multicolumn{6}{c}{**KEGG Pathway**} \\ \hline Category & Count & \(p\)-value & Category & Count & \(p\)-value \\ \hline \multicolumn{6}{c}{hsa05215:Prostate cancer ES: 2.83} & 5 & 5.32 \(\times\) 10\({}^{-4}\) \\  & & & hsa05222:Small cell lung cancer ES: 2.83 & 4 & 0.006 \\  & & & hsa05200:Pathways in cancer ES: 2.37 & 9 & 2.03 \(\times\) 10\({}^{-4}\) \\  & & & hsa05215:Prostate cancer ES 1.91 & 5 & 5.32 \(\times\) 10\({}^{-4}\) \\ \hline \hline \end{tabular} ES: Enrichment score.  
\end{table} 
Table 1: Functional annotation clustering of let-7f-5p and miR-205-5p targets.