Bioinformatics analysis of the role of RNA modification regulators in polycystic ovary syndrome.

Purpose: Polycystic ovary syndrome (PCOS) is the most common metabolic and endocrine disorder affecting women of reproductive age. The pathogenesis of PCOS is influenced by factors such as race, genetics, environment, hyperandrogenemia, hyperinsulinemia, and obesity. However, the molecular mechanisms linking RNA modification and PCOS remain underexplored. This study aims to investigate the potential genetic and molecular pathways connecting RNA modification with PCOS through bioinformatics analyses. Methods: The GSE34526, GSE5850, and GSE98421 datasets were obtained from the National Center for Biotechnology Information Gene Expression Omnibus database. We identified intersecting differentially expressed genes (DEGs) and RNA modification-related genes within the GSE34526 dataset and visualized the overlaps using a Venn diagram. Subsequent analyses included Gene Ontology (GO), pathway enrichment (Kyoto Encyclopedia of Genes and Genomes), gene set enrichment analysis (GSEA), gene set variation analysis (GSVA), and immune infiltration analysis. Additionally, we constructed a protein-protein interaction network as well as mRNA-miRNA, mRNA-RNA binding protein, and mRNA-transcription factor (TF) regulatory networks. The expression and receiver operating characteristic curves of hub genes were also identified. Results: The expression of several RNA modification-related DEGs (RMRDEGs) (ALYREF, NUDT1, AGO2, TET2, YTHDF2, and TRMT61B) showed significant differences in PCOS patients. GSEA and GSVA indicated that RMRDEGs were enriched in the hedgehog, MAPK, JAK STAT, and Notch pathways. Key transcription factors, including SP7, KLF8, HCFC1, IRF1, and MLLT1, were identified in the TF regulatory networks. Conclusions: These findings suggest that there are gene and miRNA profile alterations exist in PCOS patients and highlight immune-related differences. This knowledge could pave the way for new research directions in the diagnosis and treatment of PCOS.

Interference with ANXA8 inhibits the malignant progression of ovarian cancer by suppressing the activation of the Wnt/ß-catenin signaling pathway via UCHL5.

Ovarian cancer (OC), which threatens women's lives, is a common tumor of the female reproductive system. Annexin A8 (ANXA8) is highly expressed in OC. However, the mechanism of ANXA8 in OC remains unclear. This study investigated the potential mechanisms of ANXA8 in OC. The expression of ANXA8 in OC cells was determined by qRT-PCR and western blotting. ANXA8 interference plasmid was constructed. Moreover, CCK-8, EDU staining, TUNEL staining, western blotting, wound healing, and transwell assays were used to detect cell proliferation, apoptosis, migration, and invasion, respectively. Next, the relationship between ANXA8 and ubiquitin C-terminal hydrolase L5 (UCHL5) was verified through Co-IP. Finally, western blotting was used to detect the expression of Wnt/ß-catenin signaling-related proteins. Additionally, we further interfered ANXA8 in nude mice with OC, and detected the expression of ANXA8, UCHL5 and the signaling pathway-related proteins by immunohistochemistry and western blotting. Our results suggested that ANXA8 expression was significantly increased in OC cells. ANXA8 interference significantly attenuated the proliferative, invasive, and migratory capabilities and promoted the apoptotic ability of OC cells. Moreover, the expression of UCHL5 in OC was significantly increased. ANXA8 bound to UCHL5 in OC cells. Knockdown of ANXA8 attenuated OC cell malignant progression by downregulating the expression of UCHL5. Furthermore, ANXA8 affected the expression of Wnt/ß-catenin signaling pathway-related proteins in OC cells via UCHL5. Collectively, ANXA8 interference suppressed the activation of Wnt/ß-catenin signaling pathway via UCHL5 to inhibit cell proliferation, invasion, migration and induce cell apoptosis in OC, thus presenting a potential therapeutic strategy for OC treatment.

A novel mutation Hb jiangnan[ß3(NA3) Leu→Lys, HBB:c.10-_11delinsAA] causing elevated Hb A2 level.

OBJECTIVES: To report the hematolgocial and molecular features of a nove ß-globin variant in a Chinese fimaly. METHODS: The proband was a 19-year-old Chinese man whose Hb analysis by HPLC for thalassemia revealed an abnormal peak. Hb analysis was performed by HPLC and CE. Gap-PCR and PCR-reverse dot blot hybridization (PCR-RDB) were used to detect the common mutations in Chinese population. DNA sequencing was used to determine the Hb variant. RESULTS: The Hb variant and Hb A can be separated but co-elutes with Hb F by the CE method. However, the variant can be separated from Hb A0, Hb F, and Hb A2 using HPLC. DNA sequencing showed a mutation of codon 3 in the ß-globin gene. His wife's HPLC revealed a high value of Hb A2, which proved to be the Hb E using PCR-RDB. CONCLUSION: It was the first report of the mutation, so we named it Hb Jiangnan according to the place of residence of the proband. It can be separated by HPLC but not CE. Hb Jiangnan can cause an increased level of Hb A2.