Network-based pharmacological study of the mechanism of kaiyuzhongyutang in the treatment of tubal fimbria obstruction.

To apply a network pharmacological approach to explore the targets and possible mechanisms of Kai Yu Zhong Yu Tang (KYZYT) in the treatment of tubal fimbria obstruction. The target information of KYZYT was extracted from TCMSP and HERB database. Genes related to tubal fimbria obstruction were searched using the GENECARD database. Target protein network maps (PPI) were drawn using string database analysis and Cytoscape 3.7.1 software. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis and gene function analysis (GO) enrichment analysis were performed with the help of Perl language and biological program package in R language. To explore the multiple pharmacological mechanisms of action of KYZYT in the interventional treatment of tubal fimbria obstruction and to lay the foundation for further experimental validation. Through the collection and analysis of multiple databases, 355 biological targets of KYZYT were identified. 168 targets of tubal fimbria obstruction were obtained from disease database. The "drug-component" and "drug-target" networks of KYZYT were constructed, and the protein interaction network (PPI) of overlapping targets was analyzed to identify the key targets of the drug affecting the disease. In addition, KEGG pathway analysis and GO enrichment analysis were performed on the overlapping targets to explore the mechanism of KYZYT in the treatment of tubal fimbria obstruction. KYZYT has the characteristics of multi-component, multi-target and multi-pathway in the treatment of tubal fimbria obstruction, which provides new ideas and scientific basis for further clarification of the molecular mechanism.

RNA-binding protein IGF2BP2 enhances circ_0000745 abundancy and promotes aggressiveness and stemness of ovarian cancer cells via the microRNA-3187-3p/ERBB4/PI3K/AKT axis.

BACKGROUND: Circular RNAs (circRNAs) are increasingly recognized as important regulators in cancer including ovarian cancer (OC). This work focuses on the effects of circ_0000745 on the OC development of and molecules involved. METHODS: Expression of circ_0000745 in collected OC tissues and the acquired OC cell lines was examined by RT-qPCR. The stability of circ_0000745 in cells was examined by RNase R treatment. The target transcripts interacted with circ_0000745 were predicted using bioinformatic systems. Gain- and loss-of-function studies of circ_0000745, microRNA (miR)-3187-3p and erb-b2 receptor tyrosine kinase 4 (ERBB4) were conducted to determine their functions on proliferation, migration, invasion and stem cell property of OC cells. RESULTS: Circ_0000745 and ERBB4 were abundantly expressed while miR-3187-3p was poorly expressed in OC tissues and cells. Circ_0000745 sequestered miR-3187-3p and blocked its repressive effect on ERBB4. Downregulation of circ_0000745 reduced proliferation, aggressiveness, epithelial-mesenchymal transition, and stemness of SK-OV-3 cells, but this reduction was blocked upon miR-3187-3p inhibition or ERBB4 upregulation. By contrast, artificial induction of circ_0000745 upregulation, miR-3187-3p upregulation and ERBB4 downregulation led to inverse trends in ES-2 cells. ERBB4 promoted the phosphorylation of the PI3K/AKT signaling pathway. An RNA binding protein IGF2BP2 was found to circ_0000745 bind to and promote its expression and stability. CONCLUSION: This study demonstrated that circ_0000745 upregulated by IGF2BP2 promotes aggressiveness and stemness of OC cells through a miR-3187-3p/ERBB4/PI3K/AKT axis. Circ_0000745 may serve as a promising target for OC treatment.