ABSTRACT
MicroRNAs (miRNAs) are small noncoding RNAs that regulate gene expression at a post-transcriptional level. We examined the role of miR-126 in granulosa cell tumor (GCT) of the ovaries. In tissues from malignant GCT patients miR-126 expression was repressed. We showed that miR-126 could inhibit proliferation, migration, hormone production and promote apoptosis of cancerous granulosa cells (GCs) in vitro. The role of miR-126 as "tumor suppressor" was confirmed by using a tumor formation model in vivo. By RNA-seq, immunohistochemical staining (IHC), Western blot and luciferase reporter assay, we identified and confirmed EGFL7 as a direct functional target of miR-126 in cancer GCs. Furthermore, we found that the AKT signaling pathway was associated with miR-126 and EGFL7 in cancer GCs. Taken together, our results demonstrate a function of miR-126 in the suppression of GCT development via the regulation of EGFL7.
ABSTRACT
The granulosa cell (GC) is a critical somatic component of the ovary. It is essential for follicle development by supporting the developing oocyte, proliferating and producing sex steroids and disparate growth factors. Knowledge of the GC's function in normal ovarian development and function, and reproductive disorders, such as polycystic ovary syndrome (PCOS) and premature ovarian failure (POF), is largely acquired through clinical studies and preclinical animal models. Recently, microRNAs have been recognized to play important regulatory roles in GC pathophysiology. Here, we examine the recent findings on the role of miRNAs in the GC, including four related signaling pathways (Transforming growth factor-ß pathway, Follicle-stimulating hormones pathway, hormone-related miRNAs, Apoptosis-related pathways) and relevant diseases. Therefore, miRNAs appear to be important regulators of GC function in both physiological and pathological conditions. We suggest that targeting specific microRNAs is a potential therapeutic option for treating ovary-related diseases, such as PCOS, POF, and GCT.
