STAT3 Promotes Apoptosis of Alveolar Epithelial Cells by Inhibiting AKT Signaling

Abstract

Type II alveolar epithelial cells are a crucial component of alveolar epithelium, and transcriptional activator 3 (STAT3) have functions in regulating alveolar epithelial cell proliferation. Therefore, based on the modular approach, we analyzed the effects of silencing STAT3 on type II alveolar epithelial cells and studied its mechanism of action. Initially, in the GEO database, we downloaded data on type II alveolar epithelial cells. For transcript to me data in alveolar epithelial cell samples, we performed a differential analysis. Secondly, protein interaction network analysis (PPIs) were performed on the differential genes, and the PPIs were analyzed modularly. The module gene was subjected to enrichment analysis of GO function and KEGG pathway. Non-coding RNAs and transcription factors that regulate the module are predicted based on hyper geometric testing. Thus, we have a total of 13 dysfunction modules. These modular genes are significantly involved in biological processes such as nuclear membranes, embryonic organ development, and regulate the insulin signaling pathway and the PI3K-Akt signaling pathway substantially. We identified vital ncRNA pivots (miR-205-5p) and TF pivot (Eomes, Etsl, Nfkbl, Spi1, Statl, Usfl) to regulate dysfunction modules significantly. Our work deciphered a co-expression network that involved essential gene regulation of type II alveolar epithelial cell apoptosis. It helps to reveal the regulation of silencing STAT3 gene on alveolar epithelial cell apoptosis and deepen our understanding of the mechanism. More importantly, we explained that the silencing gene STAT3 inhibits the apoptosis of alveolar epithelial cells by activating the AKT signaling pathway, providing a new theoretical reference for the study of alveolar epithelial cells.