MicroRNA-126 Is a Tumor Suppressor of Granulosa Cell Tumor Mediated by Its Host Gene EGFL7.

Jiajie Tu,Gang Lu,Clement Leung-Kwok Chan,Wai-Yee Chan,Hoi-Hung Cheung,Zijiang Chen

doi:10.3389/fonc.2019.00486

Jiajie Tu, Gang Lu + Show 4 more

Open Access

https://doi.org/10.3389/fonc.2019.00486

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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.

Highlights

Ovarian cancer is one of the most common types of cancer in women
The expression level of miR-126 in clinical specimens obtained from a biobank of a granulosa cell tumor (GCT) cohort was analyzed using fluorescence in situ hybridization (FISH)
Our results showed that miR-126 expression was significantly lower in both malignant and benign GCT tissues than in non-cancerous ovarian cyst material (Figure 1A)

Summary

INTRODUCTION

Ovarian cancer is one of the most common types of cancer in women. It has a poor general prognosis of survival due to the generally late diagnosis [1]. GCT accounts for about 5% of all ovarian cancers with a high rate of recurrence but the pathogenesis of this form is not well understood It is essential for prognosis and therapy of GCT patients to understand the underlying pathogenic mechanisms of GCT. MiRNAs are active in drug resistance during chemotherapy and their involvement in the development of epithelial ovarian cancer (EOC) has been deduced from a number of gene profiling studies [5]. Our data suggest a critical, physiological role for miR-126 in the GCT oncology. It may be utilized as a prognostic marker or a therapeutic target for GCT treatment

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