ABSTRACT
BACKGROUND: Previous studies evaluating the association between circulating neutrophil gelatinase-associated lipocalin (NGAL) and the risk of preeclampsia (PE) showed inconsistent results. A systematic review and meta-analysis was performed to summarize the relationship between circulating NGAL and PE. METHODS: Studies comparing the circulating NGAL between pregnant women with PE and controls with no PE were found by searching Medline, Web of Science, Cochrane's Library, and Embase. Pooling results was performed using a random-effects model incorporating heterogeneity. RESULTS: In the study, 1293 women with PE and 1773 healthy pregnant women were enrolled in 18 case-control studies, and the gestational age was matched between cases and controls. Pooled results showed that compared to controls, women with PE had a significantly higher blood level of NGAL (standardized mean difference [SMD]: 0.95, 95% confidence interval [CI]: 0.63-1.28, p < .001; I2 = 92%). Subgroup analyses showed consistent results in studies of NGAL measured at the first (SMD: 0.47, 95% CI: 0.15-0.80, p = .004), the second (SMD: 0.87, 95% CI: 0.55-1.19, p < .001), and the third trimester (SMD: 1.06, 95% CI: 0.63-1.24, p < .001) of pregnancy. In addition, women with mild (SMD: 0.78, 95% CI: 0.13-1.44, p = .02) and severe PE (SMD: 1.19, 95% CI: 0.40-1.97, p = .003) both had higher circulating NGAL as compared to controls. CONCLUSIONS: High circulating NGAL is associated with PE, which may be independent of the trimesters for blood sampling and the severity of PE.
Subject(s)
Pre-Eclampsia , Female , Humans , Pregnancy , Biomarkers , Lipocalin-2 , Pre-Eclampsia/diagnosis , Pregnancy Trimester, Third , Pregnancy TrimestersABSTRACT
Circular RNAs (circRNAs) are a class of non-coding RNAs with a unique covalently closed loop structure. Recent studies indicate that dysregulation of circRNAs acts a role in cancer progression and chemotherapy resistance via interacting with RNA-binding proteins (RBPs). Herein, we identified circPBX3 to be involved in cisplatin resistance of ovarian cancer. In our study, two cisplatin-resistant ovarian cancer cell lines were established, and transcriptome RNA-sequencing was performed and circPBX3 was identified as significantly upregulated circRNA in these cells. The characteristics of circPBX3 and potential function of circPBX3 were evaluated. We found that circPBX3 was upregulated in ovarian tumor tissues and cisplatin-resistant ovarian cancer cells. CircPBX3 overexpression increased the half maximal inhibitory rate (IC50) of cisplatin, promoted colony formation and tumor xenografts growth, and reduced cell apoptosis of ovarian cancer cells under cisplatin treatment, while silencing circPBX3 showed opposite effects. Furthermore, circPBX3 could interact with the RNA-binding protein IGF2BP2, thus increased the stability of ATP7A mRNA and elevated ATP7A protein level. In addition, silencing ATP7A in ovarian cancer cells abrogated the effect of circPBX3 overexpression on cisplatin tolerance. Our findings provided a novel role of circPBX3 in cisplatin resistance of ovarian cancer.
