IGF2BP3­stabilized SIX4 promotes the proliferation, migration, invasion and tube formation of ovarian cancer cells.

The mortality rate of ovarian cancer (OC) is the highest among the different types of female reproductive system cancers. SIX homeobox 4 (SIX4), a member of the homeobox family, subfamily SIX, fulfills an important role in metastasis and angiogenesis in a variety of types of cancer. The aim of the present study was to investigate both the effects and the underlying mechanism of SIX4 on angiogenesis in OC. The Gene Expression Profiling Interactive Analysis and Encyclopedia of RNA Interactomes databases were employed to predict the expression levels of SIX4 in OC tissues, and its association with the overall survival (OS) rate of patients with OC. The expression levels of SIX4 in OC cell lines were detected by reverse transcription­quantitative PCR (RT­qPCR) and western blot analysis. Following silencing of SIX4, the proliferation, invasion, migration and angiogenesis of OC cells were investigated via Cell Counting Kit­8, colony formation, wound healing, Transwell and tube formation assays. Subsequently, the levels of insulin­like growth factor 2 mRNA binding protein 3 (IGF2BP3) in OC cell lines were detected by RT­qPCR and western blot analysis. The ability of IGF2BP3 to bind to SIX4 mRNA was detected via an RNA immunoprecipitation assay, and the stability of SIX4 mRNA was assessed by RT­qPCR following Actinomycin D treatment. Finally, the effects of transfection of sh­SIX4 and overexpression of IGF2BP3 simultaneously were examined to further delineate the mechanism involved. It was revealed that SIX4 was highly expressed in OC tissues and cells, and its expression was associated with low OS rates in patients with OC. SIX4 knockdown with short hairpin RNA inhibited the proliferation, migration and invasion of cells, as well as angiogenesis. In addition, IGF2BP3 overexpression led to an improvement in the stability of SIX4 mRNA. Overexpression of IGF2BP3 also reversed the inhibitory effect of SIX4 interference on the malignant phenotypes of OC cells. Taken together, the results of the present study demonstrated that IGF2BP3­stabilized SIX4 promoted the proliferation, metastasis and angiogenesis of SKOV3 cells.

Reproductive Health in First-degree Relatives of Patients With Polycystic Ovary Syndrome: A Review and Meta-analysis.

CONTEXT: Polycystic ovary syndrome (PCOS) is a highly heritable disease. Emerging evidence elucidated the elevated prevalence of reproductive abnormalities in first-degree relatives (FDRs) of patients with PCOS. OBJECTIVE: To explore the reproductive health in FDRs of patients with PCOS. METHODS: Ten databases were searched in December 2020 (PubMed, Embase, Web of Science, Cochrane Central Register of Controlled Trials, ClinicalTrials.gov, Chinese Biological Medical Literature, Chinese National Knowledge Infrastructure, Chinese Journals Full-text Database, WanFang, and World Health Organization international clinical trials registry platform). This study included cohort, case-control, or cross-sectional studies. The Preferred Reporting Items for Systematic Reviews and Meta-Analysis statement was followed. Dichotomous data from each of the eligible studies were combined by the Mantel-Haenszel model. Standard mean differences with 95% CIs were assessed. Heterogeneities were assessed using I2 statistics, and the quality of evidence was evaluated by a US Agency for Healthcare Research and Quality Evidence-based Practice Center program and Grading of Recommendations, Assessment, Development and Evaluation approach. RESULTS: Thirty-eight studies were included. The prevalence of PCOS (0.22; 95% CI, 0.16 to 0.29), menstrual irregularities (0.28; 95% CI, 0.22 to 0.34, P < .01), and ovary morphological changes were elevated in female PCOS FDRs. Female FDRs also presented with increased levels of luteinizing hormone, total testosterone (standard mean difference, 0.53; 95% CI, 0.28 to 0.78, P < .01), unconjugated testosterone, free androgen index, dehydroepiandrosterone sulfate (DHEAS), and antimüllerian hormone levels. Subgroup analyses indicated that some of these changes begun in pubertal girls. Furthermore, fathers of PCOS patients had a higher risk of premature baldness. The DHEAS level was elevated in male FDRs. CONCLUSION: The findings of this analysis suggested that FDRs of patients with PCOS suffered from reproductive endocrinological dysregulations. Thus, more attention should be focused on this population.