miRNA expression profiling in formalin-fixed paraffin-embedded endometriosis and ovarian cancer samples

Abstract

Endometriosis is an inflammatory pathology associated with a negative effect on life quality. Recently, this pathology was connected to ovarian cancer, in particular with endometrioid ovarian cancer. microRNAs (miRNAs) are a class of RNA transcripts ~19–22 nucleotides in length, the altered miRNA pattern being connected to pathological status. miRNAs are highly stable transcripts, and these can be assessed from formalin-fixed paraffin-embedded (FFPE) samples leading to the identification of miRNAs that could be developed as diagnostic and prognostic biomarkers, in particular those involved in malignant transformation. The aim of our study was to evaluate miRNA expression pattern in FFPE samples from endometriosis and ovarian cancer patients using PCR-array technology and also to compare the differential expression pattern in ovarian cancer versus endometriosis. For the PCR-array study, we have used nine macrodissected FFPE samples from endometriosis tissue, eight samples of ovarian cancers and five normal ovarian tissues. Quantitative real-time PCR (qRT-PCR) was used for data validation in a new patient cohort of 17 normal samples, 33 endometriosis samples and 28 ovarian cancer macrodissected FFPE samples. Considering 1.5-fold expression difference as a cut-off level and a P-value <0.05, we have identified four miRNAs being overexpressed in endometrial tissue, while in ovarian cancer 15 were differentially expressed (nine overexpressed and six downregulated). The expression level was confirmed by qRT-PCR for miR-93, miR-141, miR-155, miR-429, miR-200c, miR-205 and miR-492. Using the interpretative program Ingenuity Pathway Analysis revealed several deregulated pathways due to abnormal miRNA expression in endometriosis and ovarian cancer, which in turn is responsible for pathogenesis; this differential expression of miRNAs can be exploited as a therapeutic target. A higher number of altered miRNAs were detected in endometriosis versus ovarian cancer tissue, most of them being linked with epithelial-to-mesenchymal transition.

The Role of microRNAs in Epithelial Ovarian Cancer Metastasis

“…Therefore, comparison between tumor tissues and normal ovarian tissues may not provide accurate information about miRNA dysregulation. A recent study compared miRNA expression profiles between endometriosis and EOC tissues and suggested the potential role of miR-93, miR-325, and miR-492 in the malignant transformation of endometriosis to EOC [ 123 ]. Further investigation of miRNA expression in different subtypes in comparison with their tissues of origin would provide insights into their diagnostic and/or prognostic significance.…”

The Endometriotic Tumor Microenvironment in Ovarian Cancer

“…Studies have shown that miRNAs are frequently dysregulated in endometriosis and endometriosis-associated ovarian cancers (reviewed in [ 53 , 54 , 55 ]). Compilation of dysregulated miRNAs in ovarian endometrioid and clear-cell adenocarcinomas, as well as endometriosis ( Supplemental Table S1 ) shows dysregulated miRNA molecules for each tissue type [ 53 , 55 , 124 , 125 , 126 , 127 , 128 , 129 , 130 , 131 , 132 , 133 ]. Figure 2 shows the number of miRNAs dysregulated in ovarian clear-cell and endometrioid adenocarcinomas, and endometriosis tissues.…”

“…Endometrioid ovarian cancer had the shortest list of dysregulated miRNAs ( Figure 2 and Supplemental Table S1 ). MiR-200 family miRNAs (miR-200a, -200b, -200c, -141, and -429) were upregulated in ovarian cancer and may play crucial roles in ovarian cancer metastasis, diagnosis, and treatment [ 126 , 129 , 130 , 138 ].…”

Myocardial hypertrophy is improved with berberine treatment via long non-coding RNA MIAT-mediated autophagy

“…Non‐coding RNAs (ncRNAs) lack the capacity of coding proteins and mainly include small non‐coding RNAs (sncRNAs, shorter than 200 nucleotides) and long non‐coding RNA (lncRNAs, longer than 200 nucleotides) . The sncRNAs mainly contain microRNAs (miRNAs), which could bind to the 3′ untranslated region of the targeting mRNA and inhibit translation or stimulate mRNA degradation . Previous studies have proved that miRNAs are involved in biological processes of many diseases .…”