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

MicroRNAs (miRNAs) are small noncoding RNAs that play important roles in gene regulation at post-transcriptional level. In the current study, we examined the effect of miR-126 on granulosa cell tumor (GCT), a subtype of ovarian cancer. miR-126 expression was repressed in tissues from malignant GCT patients. We showed that miR-126 could inhibit cell proliferation, migration/invasion, ovarian hormone production and promote anticancer drug-induced apoptosis in vitro. The ‘tumor suppressor’ role of miR-126 was further validated in an mice GCT 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 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 repression of GCT development via regulating EGFL7.
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research

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Establishing reliable prognostic factors as well as specific targets for new therapeutic approaches is an urgent requirement in advanced ovarian cancer. For several tumor entities, the ubiquitously spread scaffold protein β-arrestin 2, a multifunctional scaffold protein regulating signal transduction and internalization of activated G protein-coupled receptors (GPCRs), has been considered with rising interest for carcinogenesis. Therefore, we aimed to elucidate the prognostic impact of β-arrestin 2 and its functional role in ovarian cancer. β-arrestin 2 expression was analyzed in a subset of 156 samples of o...
Source: Frontiers in Endocrinology - Category: Endocrinology Source Type: research
AbstractAnti-M üllerian Hormone (AMH) is critical for physiologic involution of the Mullerian ducts during sexual differentiation in the male fetus. In women, AMH is a product of the small antral follicles in the ovaries and serves to function as an autocrine and paracrine regulator of follicular maturation. As t he size of the residual follicular pool depends on the quantity of small antral follicles and declines over time, the serum AMH level in women follows a characteristic trajectory: a gradual decline throughout the reproductive years and a precipitous drop at menopause, becoming undetectable soon afte r. Thus, ...
Source: The Journal of Obstetrics and Gynecology of India - Category: OBGYN Source Type: research
Only one of seven eligible patients underwent intraperitoneal chemotherapy in our large heterogenous health system. Intraperitoneal chemotherapy use has been associated with improved 10 ‐year survival, but not necessarily recurrence benefit compared to intravenous chemotherapy. AbstractBackgroundIntraperitoneal/intravenous chemotherapy (IP/IV) was associated with improved survival for ovarian cancer (OC) patients in several randomized clinical trials. However, the uptake of IP/IV in clinical practice is varied due to conflicting evidence about its impact on survival and recurrence. The aim of this study was to explore th...
Source: Cancer Medicine - Category: Cancer & Oncology Authors: Tags: ORIGINAL RESEARCH Source Type: research
Contributor : Paul A CloosSeries Type : Expression profiling by high throughput sequencing ; Genome binding/occupancy profiling by high throughput sequencingOrganism : Homo sapiensThe FOXL2 mutant C134W occurs in virtually all adult ovarian granulosa cell tumors (AGCT), and is considered a driver of oncogenesis in this disease. However, the mechanism by which FOXL2C134W contributes to tumorigenesis is not known. Here, we show that mutant FOXL2C134W acquires the ability to bind SMAD4, forming a FOXL2C134W/SMAD4/SMAD2/3 complex that binds a novel hybrid DNA motif AGHCAHAA, unique to the FOXL2C134W mutant. This binding induce...
Source: GEO: Gene Expression Omnibus - Category: Genetics & Stem Cells Tags: Expression profiling by high throughput sequencing Genome binding/occupancy profiling by high throughput sequencing Homo sapiens Source Type: research
Gourley The estrogen receptor (ER) has functionality in selected ovarian cancer subtypes and represents a potential target for therapy. The majority (>80%) of high grade serous, low grade serous and endometrioid carcinomas and many granulosa cell tumors express ER-alpha (ERα), and these tumor types have demonstrated responses to endocrine therapy (tamoxifen and aromatase inhibitors) in multiple clinical studies. Biomarkers of responses to these drugs are actively being sought to help identify responsive cancers. Evidence for both pro-proliferative and pro-migratory roles for ERα has been obta...
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Review Source Type: research
In this study, potentially targetable genomic alterations in AGCTs were investigated by whole genome sequencing on 46 tumor samples and matched normal DNA. Copy number variant (CNV) analysis confirmed gain of chromosome 12 and 14, and loss of 22. Pathogenic TP53 mutations were identified in three patients with highest tumor mutational burden and mitotic activity, defining a high-grade AGCT subgroup. Within-patient tumor comparisons showed 29–80% unique somatic mutations per sample, suggesting tumor heterogeneity. A higher mutational burden was found in recurrent tumors, as compared to primary AGCTs. FOXL2-wildtyp...
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Article Source Type: research
et A, Berton D, Kalbacher E, Chakiba C, Meeus P, Selle F, Treilleux I, Lecuru F, Pautier P, Ray-Coquard I Abstract OBJECTIVE: The French national rare gynecological tumor network has been established to improve the quality of care through offering expertise in double reading histological diagnosis, reviewing cases and guiding management of these tumors through specialized multidisciplinary tumor boards and online clinical guidelines (www.ovaire-rare.com). The aim of this study is to evaluate the impact of the development and implementation of this network by assessing the conformity of medical practice with the gu...
Source: Gynecologic Oncology - Category: Cancer & Oncology Authors: Tags: Gynecol Oncol Source Type: research
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Source: Toxicology in Vitro - Category: Toxicology Authors: Tags: Toxicol In Vitro Source Type: research
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Source: Journal of Cancer Research and Therapeutics - Category: Cancer & Oncology Authors: Source Type: research
ConclusionThis study demonstrates that rAMH is bioactive in the ovary for a limited time, and that pharmacological administration of rAMH during chemotherapy treatment reduces follicle activation and primordial follicle loss and significantly improves reproductive outcomes in a mouse model, and does not interfere with the therapeutic actions of the treatment. Further investigation is necessary to determine whether it has similar protective effects in the human ovary.
Source: Journal of Assisted Reproduction and Genetics - Category: Reproduction Medicine Source Type: research
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