Identification of driver genes and key pathways of prolactinoma predicts the therapeutic effect of genipin

Abstract

The purpose of the present study was to identify the potential targets and markers for diagnosis, therapy and prognosis in patients with prolactinoma at the molecular level and to determine the therapeutic effects of genipin in prolactinoma. The gene expression profiles of GSE2175, GSE26966 and GSE36314 were obtained from the Gene Expression Omnibus database. The differentially expressed genes (DEGs) were identified after comparing between gene expression profiles of the prolactinoma tissues and normal tissues. Then, Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis and protein-protein interaction (PPI) network analysis were conducted. In addition, in vitro , scratch assay, colony-forming assay, Cell Counting Kit 8 (CCK8) assay and flow cytometry were performed to verify the functional effects of genipin. An aggregate of 12,695, 3,847 and 5,310 DEGs were identified from GSE2175, GSE26966 and GSE36314, respectively. The results of GO and KEGG analysis showed that the DEGs significant and important for prolactinoma were mostly involved with ‘spindle pole’ and ‘oocyte meiosis’. A total of 20 genes were selected as hub genes with high degrees after PPI network analysis, including mitogen-activated protein kinase 1 (MAPK1), MYC, early growth response 1 (EGR1), Bcl2 and calmodulin 1 (CALM1). CCK8 assay, colony-forming assay and scratch assay were performed to verify the anti-prolactinoma effect of genipin. The results of flow cytometry showed that apoptosis was increased by genipin. MAPK1, MYC, EGR1, Bcl2 and CALM1 were screened as main hub genes. Genipin upregulated the expression level of EGR1 and p21 (downstream mediator of EGR1) and EGR1, inhibited the proliferation and migration of prolactinoma cells. Genipin is a promising drug for treatment of patients with prolactinoma.

Genipin, an Inhibitor of UCP2 as a Promising New Anticancer Agent: A Review of the Literature

“…Zhong et al reported that, in prolactinoma cells, genipin upregulated the expression levels of EGR1 and p21 (a downstream mediator of EGR1), with EGR1 inhibiting the proliferation, migration, and induction of prolactinoma cell apoptosis [ 75 ].…”

Network Analysis and Experimental Verification of the Mechanisms of Hydroxysafflor Yellow A in Ischemic Stroke Following Atherosclerosis

“…The selected genes between HSYA and ISFA were input into the STRING (https:// string-db.org/ (accessed on 22 January 2022)) database [26] for protein-protein interaction (PPI) network analysis. Proteins at a minimum required interactions with a confidence score ≥ 0.9.…”

Novel Findings regarding the Bioactivity of the Natural Blue Pigment Genipin in Human Diseases

“…Zhang et al [ 54 ] suggest that genipin (1, 1.25, and 5 mg/kg) protects against LPS-induced acute lung injury by inhibiting the NFκB and NLR family pyrin domain containing 3 (NLRP3) signaling pathways in mice. In addition, 2 and 5 mg/kg genipin appears to protect against apoptosis and inflammation in LPS-induced acute lung injury by promoting autophagy [ 55 ].…”