Targeting EGR1 showed potential therapeutic effects on prolactinoma

Abstract:

Objective：To explore the differentially expressed genes in patients with prolactinoma（PRL） from the molecular level of genes，for studying the core driving gene of disease development；to provide potential targets for clinical diagnosis，treatment and prog－nosis in patients with RPL and predict molecular targeted drugs for treating patients with RPL by focusing on core driving genes. Methods：Gene expression profile data of PRL patients were obtained from the gene expression omnibus（GEO） database，and the differentially expressed genes（DEG） of PRL tissues and normal tissues were screened. At the same time，weighted gene co-expression network analysis（WGCNA） and protein-interaction analysis（PPI） were used to determine the core driver genes of PRL development. At the same time，gene ontology（GO） analysis，Kyoto Encyclopedia of Genes and Genomes（KEGG ） analysis and gene set enrichment analysis（GSEA） were conducted to explore the altered biological functions and signaling pathways in PRL patients，and to explore the molecular mechanism of tumor development. In addition，in vitro wound-healing test，clone formation assays，CCK-8 assays and flow cytometry experiments were performed to validate potential therapeutic effects of molecular-targeted drugs. Results：A total of 1 201 differentially expressed genes were identified，of which EGR1，MAPK1，MYC，BCL2 and CALM1 were important. The results of GO and KEGG analysis indicated that the formation of PRL was mainly related with changes of spindle pole and influenced oocyte meiosis. PRL was likely to have some homology with Parkinson’s disease. Simultaneously，CCK-8 assay，clone formation assay and in vitro wound-healing test confirmed that EGR1 agonist of Genipin had potential effect on anti-prolactinoma. Results of flow cytometry analysis showed that the apoptosis percentage of tumor cells was increased as the dose of Genipin increased. Conclusion：EGR1，MAPK1，MYC，BCL2 and CALM1 are core driving genes of PRL，which have important impacts on the PRL development. Genipin，an agonist of EGR1，inhibiting the proliferation and migration of PRL cells in vitro，shows a potential therapeutic effect on PRL. At the same time，this study screened a high-risk signal－ing pathway for the PRL development，providing a new target for clinical diagnosis and treatment，with great significance.