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

Front Oncol. 2019 Jun 11:9:486. doi: 10.3389/fonc.2019.00486. eCollection 2019.

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.

Keywords: AKT pathway; EGFL7; GCT; miR-126; tumoriogenesis.