IGF2BP2 promotes the progression of ovarian endometriosis by regulating m6A-modified MEIS2 and GATA6.

BACKGROUND: m6A-RNA modification mediated by the N6-methyladenosine RNA methylation-related molecule methyltransferase-like 3 has been implicated in the progression of endometriosis. However, the functions of other m6A regulators, especially in ovarian endometriosis, remain unknown. METHODS: Three datasets (GSE7305, GSE7307, and GSE37837) with diagnosed ovarian endometriosis were extracted from the Gene Expression Omnibus database. Using bioinformatics methods such as Weighted Gene Co-expression Network Analysis, Gene Ontology analysis, protein-protein interaction, and correlation, hub genes were identified. Using dot blot and N6-methyladenosine-IP-qPCR, the total and individual N6-methyladenosine gene levels were quantified. On clinical ovarian ectopic and eutopic endometrium tissues, N6-methyladenosine RNA methylation sequencing was performed. To authenticate protein localization and expression level, immunohistochemical staining and western blot were conducted, respectively. The database Connectivity Map was used to predict small molecules with potential therapeutic effects. RESULTS: In ovarian endometriosis, the N6-methyladenosine "reader" molecule IGF2BP2 and related target genes MEIS2 and GATA6 were highly expressed. IGF2BP2 promoted the proliferation, migration, and invasion of ectopic endometrial stromal cells by stabilizing the mRNA of MEIS2 and GATA6. Synergistically, METTL3 and IGF2BP2 increased the N6-methyladenosine methylation of MEIS2 and GATA6. We developed five molecules (Mercaptopurine, MK-886, CP-863187, Canadine, and Securinine) that could be used to treat ovarian endometriosis based on IGF2BP2. CONCLUSION: Our findings provided additional support for a systematized understanding of the role of N6-methyladenosine RNA methylation in endometriosis and confirmed for the first time the mechanism of IGF2BP2 in promoting ovarian endometriosis. This provides the molecular foundation for potential future therapies for ovarian endometriosis. DATA AVAILABILITY: The data used to support the findings of this study are available from the corresponding author upon request.

Pregnancy anxiety scale:development,reliability and validity / 中华行为医学与脑科学杂志

Objective To develop anxiety scale suitable for Chinese pregnant women and evaluate its reliability and validity. Methods Based on existing research results and clinical experience,this study compiled pregnancy anxiety scale(PAS). A sample of 509 pregnant women were selected for investigation and 65 of them were randomly retested for test-retest reliability with 2 week interval. Item analysis was con-ducted to screen valid items. Then the construct validity of the scale was tested by exploratory factor analysis ( EFA) and confirmatory factor analysis(CFA). Finally the reliability and criterion validity of the scale were evaluated using Cronbach's α coefficient,retest reliability coefficient and Pearson correlation coefficient. Re-sults The PAS was composed of 27 items in four factors,including worry about delivery,worry about them-selves,worry about fetal health and general anxiety. The four factors were extracted by EFA which could ex-plain 62. 48% of the total variance. Besides,the result of CFA demonstrated that the model fitted the data with well construct validity (χ2/df=1. 89,RMR=0. 04,RMSEA=0. 06,IFI=0. 92,TLI=0. 91,CFI=0. 92, PGFI=0. 70,PNFI=0. 74,PCFI=0. 81). The score of the pregnancy-related anxiety scale and its factors scores were positively correlated with the scores of pregnancy-related anxiety questionnaire(PAQ) and child-birth attitudes questionnaire(CAQ). The correlation coefficients were 0. 60-0. 80 and 0. 50-0. 78 respectively (all P<0. 01). The Cronbach's α coefficient was 0. 93 for the total scale and that of the four factors ranged from 0. 82 to 0. 90. The test-retest reliability was 0. 68 for the total scale and ranged from 0. 54 to 0. 75 for the four factors. Conclusion The PAS has a good reliability and validity,and it can be used as a valid tool to measure the anxiety level of pregnant women.