Effect of circadian rhythm disturbance on Benign prostatic hyperplasia in rats

Benign prostatic hyperplasia (BPH) and circadian rhythm disorders are common diseases that negatively affect quality of life and place a heavy economic burden on society. There is growing evidence that the two diseases are closely related, which may make disease outcomes worse. In this study, we aim to analyze the therapeutic potential of key genes.The effect of circadian rhythm disruption on prostate growth was investigated in animal experiments, and RNA sequencing (RNA-seq) was used to identify differentially expressed (DEGs) genes.GO, KEGG and GSEA enrichment analyses were performed for differentially differentiated genes. Construction of protein-protein interaction (PPI) networks using differentially expressed genes. QRT-PCR and Ki67 immunohistochemistry were used to validate these assay results.We demonstrated that circadian rhythm disturbance significantly increased the prostate index, increased the ratio of Ki67-positive cells, and decreased the mRNA expression of circadian genes in rats. In addition, circadian rhythm disturbances increased DHT levels and decreased E2 levels. Transcriptome analysis revealed 268 differentially expressed genes between the circadian disorder treatment group and the model group. The results of GO analysis showed that DERGs were mainly enriched in immune response, defense response to protozoa, and c-c chemokine binding. KEGG enrichment analysis is mostly performed in the immune system, Signaling molecules and interaction, Signal transduction, and Cell motility. GSEA functional enrichment analysis showed that rhythm disturbance was related to regulating cell proliferation, migration, and adhesion. In addition, a protein-protein interaction (PPI) network was constructed using differentially expressed mRNAs. Five different algorithms were used to select the top 30 differential genes, and we constructed a circular network using the genes predicted by the association between the differential genes and genemania. qRT-PCR verified 9 key genes, indicating the accuracy of the sequencing results.Through a combination of experimental and bioinformatics analysis, this study confirmed that circadian rhythm disruption led to changes in the mRNA expression of circadian genes and immune-related genes in rats, and the results of GO and KEGG analysis showed that the biological processes of differential genes and the enrichment of molecular signaling pathways were mostly concentrated in the immune system, and these genes and molecular signaling pathways may play an important role in the prostate of rats with circadian rhythm disorders.