Abstract
In human epithelial ovarian cancer (EOC), various miRNAs can function as either oncogenes or tumor suppressor genes. We investigated miRNAs known to be involved in EOC progression and analyzed their expression in tissues and serum-derived exosomes from benign serous cystadenoma, borderline serous tumor, low-grade serous ovarian cancer, and high-grade serous ovarian cancer patients (HGSO). The HGSO group was divided based on the platinum-free interval, which is defined as the duration from the completion of platinum-based chemotherapy to recurrence. We also analyzed the mRNA levels of target genes that candidate miRNAs might regulate in patient tissues. miR-214-3p was highly expressed in tissues and exosomes derived from EOC with high malignancy and also found to regulate the expression of LIM homeobox domain 6 (LHX6) mRNA. Serum exosomal levels of miR-214-3p were significantly increased in platinum-resistant HGSO (25.2-fold, p < 0.001) compared to the exosomal expression of benign tumor patients. On transfection of miR-214-3p inhibitor in EOC cells, cell proliferation was inhibited while apoptotic cell death was increased. Collectively, we suggest that miR-214-3p in serum exosomes can be a potential biomarker for the diagnosis and prognosis of ovarian tumor, and its inhibition can be a supportive treatment for EOC.
Highlights
Most ovarian cancers originate from the ovarian and fallopian tube epithelium
The total RNA extracted from each tissue was used to measure the expression of nine candidate miRNAs known to be involved in ovarian cancer progression (Figure 1). miRNA analysis revealed that the expression of miR-21-5p, miR-141-3p, miR-200a-3p, miR-200b-3p, miR-203-3p, miR-205-5p, and miR-214-3p was increased in borderline serous tumor, low-grade serous ovarian cancer (LGSO), and platinum-resistant high-grade serous ovarian cancer (HGSO) tissues compared to their expression in benign tumor (Figure 1A–D,F–H)
The results suggested that the expression of miRNAs is significantly altered with respect to ovarian tumor progression and that they can be promoted as potential biomarkers for the diagnosis of epithelial ovarian cancer (EOC)
Summary
Most ovarian cancers originate from the ovarian and fallopian tube epithelium. EOC treatment involves cytoreduction surgery followed by platinum-based chemotherapy. Most patients experience cancer recurrence within 12 to 18 months after the first treatment. Understanding the molecular mechanisms behind the malignant transformation and recurrence of EOC and developing diagnostic markers to predict poor prognosis in EOC patients are important. MicroRNAs (miRNAs) are a class of small non-coding RNAs that play a role in cell proliferation, apoptosis, and carcinogenesis by regulating target genes [2]. MiRNAs can function as either oncogenes or tumor suppressor genes [3,4]. In EOC cells, many miRNAs target specific genes and promote cell proliferation or induce apoptosis [5,6]. MiR-31 suppresses the Cancers 2019, 11, 1917; doi:10.3390/cancers11121917 www.mdpi.com/journal/cancers
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