Comparative Analysis of Cell-Free miR-205-5p, let-7f-5p, and miR-483-5p Expression in Ovarian Cell Cultures and Plasma Samples of Patients with Ovarian Cancer

Abstract

The term liquid biopsy reveals a non-invasive diagnostic method that might be based on the quantification of cell-free microRNAs in body fluids. However, the identification of candidates for liquid biopsy is challenging. Our aim was to compare the cell-free expression of miR-483-5p, miR-205-5p, and let-7f-5p in ovarian cell cultures and plasma samples of patients with ovarian cancer. Both the intracellular and cell-free expression of miR-205-5p and let-7f-5p proved to be higher in the Estrogen Receptor α (ERα) expressing PEO1 cell-line than in the estrogen non-sensitive A2780. Moreover, the expression of let-7f-5p was up-regulated in response to estradiol exposure that was diminished after the addition of an ERα selective antagonist. MiR-483-5p had lower intracellular and cell-free expression in PEO1. All these miRNAs had detectable expression level in plasma samples, among which miR-205-5p proved to be overexpressed in the plasma samples of patients with ovarian tumors compared to healthy controls and possessed an acceptable diagnostic potential with ROC-AUC 0.683 (95% CI 0.57–0.795). Functional annotation clustering of the target genes of miR-205-5p revealed several clusters involved in cancer development. We suggest that miR-205-5p might be a promising biomarker candidate in ovarian cancer that should be further analyzed in larger sample size.

Suppressing the PI3K/AKT Pathway by miR-30d-5p Mimic Sensitizes Ovarian Cancer Cells to Cell Death Induced by High-Dose Estrogen

“…The ERα-positive PEO1 cell line and the A2780 cell line that does not express ERα [ 18 ]. According to our previous studies, ERα expression strongly influenced the basal expression of miRNAs in these cell lines [ 18 , 19 ]. Based on the above findings, we further investigated the basal expression of miR-30a-3p, miR-30a-5p, miR-30d-5p, and miR-30e-5p in the PEO1 and A2780 cell lines.…”

“…These results suggest that miR-30s—especially miR-30a-5p and miR-30d-5p—might have higher biological relevance in the ERα-expressing PEO1 cell line. We also determined whether the expression of miR-30s change in response to estrogen exposure, a phenomenon that was observed in the case of some miRNAs in our previous studies [ 18 , 19 ]. In these experiments, the PEO1 cell line was treated with E2 in a 10 nM–100 µM concentration range.…”

“…The quantification was performed in triplicates. The expression of miR-103-3p was used as an internal reference that was also applied in our previous experiments [ 17 , 18 , 19 , 20 ]. The normalized expression was determined using the results of 4 independent experiments applying the 2 −ΔCt formula.…”

“…Previously, we have identified several miRNAs that might have high biological relevance in estrogen-sensitive ovarian cancer cells and are suggested to be promising non-invasive biomarkers in ovarian cancer [ 17 , 18 , 19 , 20 ]. Here, our aim was to characterize the biological relevance of miR-30 family members in ovarian cancer cells.…”

Diagnostic performance of microRNA-34a, let-7f and microRNA-31 in epithelial ovarian cancer prediction

“…Similarly, the diagnostic potential of microRNA-34a and microRNA-31 is analogous to combined microRNA panels for the early diagnosis of EOC. Recent study showed combined diagnostic value of miR-34a and CA-125 could discriminate EOC from normal with an AUC of 0.818, while lower expression of let-7f has the diagnostic value of AUC 0.78 [ 24 29 30 31 32 ]. Moreover, the comparative expression analysis of let-7f in different cancers (colorectal, lung, prostate, papillary thyroid cancer) showed a higher diagnostic value for discriminating respective cancer from the normal [ 29 31 32 33 34 35 ].…”