Yuanyuan Zhang

AIM: Findings from recent studies suggest that obesity may be associated with an increased risk of endometrial cancer, but several earlier studies were less conclusive. Here we strive to estimate this relationship in a meta-analysis of published data. METHODS: We searched Pubmed and Embase for studies on body mass index and the risk of endometrial cancer, published from 1989 to 2011. Data were independently extracted and analyzed using random or fixed effects meta-analysis depending on the degree of heterogeneity. RESULTS: Seven cohort studies and 11 case-control studies were included in the meta-analysis. Overall, the conditions of excess body weight ([EBW] defined as body mass index [BMI] ≥25 kg/m²), obesity (BMI ≥30 kg/m²) and overweight (25< BMI <30 kg/m²) were associated with an increased risk of endometrial cancer (relative risk [RR] for EBW=1.62, 95% confidence interval [CI], 1.39-1.89; for obesity RR=2.54, 95% CI, 2.11-3.06; for overweight RR=1.32, 95% CI, 1.16-1.50). Subgroup analyses showed that the positive associations were independent of study design, geographic locations, self-reported BMI, alcohol use, smoking habit, history of diabetes, hormone therapy, age at menarche, age at menopause, parity, and age at first full term pregnancy. However, there was no statistically significant association between EBW and endometrial cancer risk for measured BMI (for EBW RR=1.29, 95% CI, 0.66-2.53). CONCLUSIONS: The findings from this meta-analysis strongly support that the conditions of EBW, overweight, and obesity are all associated with an increased risk of endometrial cancer. Also, the strength of the association increases with increasing BMI.

Preeclampsia is characterized by hypertension and proteinuria twenty weeks into pregnancy. Failure of uterine spiral artery remodeling contributes to preeclampsia's development. The development might be associated with trophoblast cells functioning abnormally. Long non-coding RNAs (lncRNAs) are aberrantly expressed in many diseases. Maternally expressed gene 3 (MEG3), one of these lncRNAs, might function as a tumor suppressor. Aberrant expression of MEG3 induces prenatal death, and little is known of MEG3's role in preeclampsia. This study aims to identify the role of lncRNA MEG3 on apoptosis and the migration of human trophoblast cells, and to investigate the involvement of lncRNA MEG3 in pathogenic mechanisms underlying preeclampsia. In this study, we found MEG3 levels were down-regulated by approximately 80% in placental samples collected from preeclamptic patients (n = 30) compared to samples collected from normotensive patients (n = 30) by qRT-PCR analysis. By designing RNA interference species to suppress MEG3 and specific plasmids designed to over-express MEG3, we explored the role of MEG3 on the functions of two trophoblast cell-lines, HTR-8/SVneo and JEG3 cells. Over-expression of MEG3 reduced apoptosis and promoted migration of HTR-8/SVneo and JEG3 cells. Furthermore, inhibition of endogenous MEG3 increased apoptosis and decreased migration of HTR-8/SVneo and JEG3 cells. Additionally, lncRNA MEG3 influenced expression of NF-κB, Caspase-3, and Bax protein expressions in trophoblast cells. Our findings highlight that abnormal levels of lncRNA MEG3 might lead to aberrant conditions in HTR-8/SVneo and JEG3 trophoblast cells, which might be associated with uterine spiral artery remodeling failure and its contribution to preeclampsia.

Due to limited treatment options, pre-eclampsia (PE) is associated with fetal perinatal and maternal morbidity and mortality. During the causes of PE, failure of uterine spiral artery remodeling which might be related to functioning abnormally of trophoblast cells, result in the occurrence and progression of PE. Recently, abnormal expression of long non-coding RNAs (lncRNAs), as imperative regulators involved in human diseases progression (included PE), which has been indicated by increasing evidence. In this research, we found that TUG1, a lncRNA, was markedly reduced in placental samples from patients with PE. Loss-function assays indicated that knockdown TUG1 significantly affected cell proliferation, apoptosis, migration and network formation in vitro. RNA-seq revealed that TUG1 could affect abundant genes, and then explore the function and regulatory mechanism of TUG1 in trophoblast cells. Furthermore, RNA immunoprecipitation and chromatin immunoprecipitation assays validated that TUG1 can epigenetically inhibit the level of RND3 through binding to EZH2, thus promoting PE development. Therefore, via illuminating the TUG1 mechanisms underlying PE development and progression, our findings might furnish a prospective therapeutic strategy for PE intervention.