Abstract
Simple SummaryMiRNA-103/107-DICER axis may be one of the key regulators of cancer aggressiveness. Data on miRNA-103/107 in high grade serous ovarian cancer is scarce. We aimed to assess miRNA-103/107 expression levels in high grade serous ovarian cancer tissues and relate them to patients’ clinicopathological data. MiRNA-103/107, DICER expression levels were also evaluated in selected ovarian cancer cell lines. Clinical and prognostic significance of miRNA-103/107 was not confirmed in our study. However, the results of our study support the possible existence of miRNA-103/107- DICER axis in ovarian cancer.High levels of miRNA-103/107 are associated with poor outcomes in the case of breast cancer patients. MiRNA-103/107-DICER axis may be one of the key regulators of cancer aggressiveness. MiRNA-103/107 expression levels have never been related to patients’ clinicopathological data in epithelial ovarian cancer. We aimed to assess miRNA-103/107 expression levels in high grade serous ovarian cancer tissues. Expression levels of both miRNAs were related to the clinicopathological features and survival. We also evaluated expression levels of miRNA-103/107 and DICER in selected ovarian cancer cell lines (A2780, A2780cis, SK-OV-3, OVCAR3). We assessed the relative expression of miRNA-103/107 (quantitative reverse transcription-polymerase chain reaction) in fifty archival formalin-fixed paraffin-embedded tissue samples of primary high grade serous ovarian cancer. Then, miRNA-103/107 and DICER expression levels were evaluated in selected ovarian cancer cell lines. Additionally, DICER, N-/E-cadherin protein levels were assessed with the use of western blot. We identified miRNA-107 up-regulation in ovarian cancer in comparison to healthy tissues (p = 0.0005). In the case of miRNA-103, we did not observe statistically significant differences between cancerous and healthy tissues (p = 0.07). We did not find any correlations between miRNA-103/107 expression levels and clinicopathological features. Kaplan–Meier survival (disease-free and overall survival) analysis revealed that both miRNAs could not be considered as prognostic factors. SK-OV-3 cancer cell lines were characterized by high expression of miRNA-103/107, relatively low expression of DICER (western-blot), and relatively high N-cadherin levels in comparison to other ovarian cancer cell lines. Clinical and prognostic significance of miRNA-103/107 was not confirmed in our study.
Highlights
Ovarian cancer is characterized by a high fatality rate and is responsible for approximately 2–3%of all cancer deaths
DICER expression levels and partial loss of E-cadherin. Such findings would support the possible existence of the miRNA-103/107-DICER axis in ovarian cancer
Since we failed to show any significant clinical correlations in regard to miRNA-103/107 in high grade serous ovarian cancer, we decided to perform a preliminary and simple assessment of various cancer cell lines in order to verify the potential existence of the miRNA-103/107-DICER axis in the case of ovarian cancer
Summary
Ovarian cancer is characterized by a high fatality rate and is responsible for approximately 2–3%of all cancer deaths. Epithelial ovarian cancer (EOC) is the most common type of ovarian malignancy, as only 10% of tumors are of non- epithelial origin. Aberrant expression of miRNAs has been reported in multiple neoplasms and related to the stage of the disease or clinical outcome [5,6]. Meritt et al reported that low DICER expression was associated with advanced-stage disease and reduced median survival [8]. Martello et al identified a miRNA family (miRNA-103/107) that inhibited miRNA biosynthesis by targeting DICER [9]. They reported that high levels of miR-103/107 are associated with metastasis and poor outcome in breast cancer. Inhibition of miRNA-103/107 in malignant cells resulted in the attenuation of migratory and metastatic properties
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