Department of Neurosurgery, The First Hospital of Jilin University, Changchun, Jilin 130012, P.R. China.
Clinical College, Jilin University, Changchun, Jilin 130012, P.R. China.
Mol Med Rep. 2019 Sep;20(3):2712-2724. doi: 10.3892/mmr.2019.10505. Epub 2019 Jul 18.
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.
本研究旨在从分子水平上确定泌乳素瘤患者的诊断、治疗和预后的潜在靶点和标志物，并确定京尼平在泌乳素瘤中的治疗效果。从基因表达综合数据库中获取 GSE2175、GSE26966 和 GSE36314 的基因表达谱。比较泌乳素瘤组织和正常组织的基因表达谱后，鉴定差异表达基因（DEGs）。然后进行基因本体（GO）、京都基因与基因组百科全书（KEGG）分析和蛋白质-蛋白质相互作用（PPI）网络分析。此外，在体外通过划痕实验、集落形成实验、细胞计数试剂盒 8（CCK8）实验和流式细胞术来验证京尼平的功能作用。从 GSE2175、GSE26966 和 GSE36314 中分别鉴定出 12695、3847 和 5310 个 DEGs。GO 和 KEGG 分析结果表明，对于泌乳素瘤而言，具有显著意义和重要性的 DEGs 大多与“纺锤体极”和“卵母细胞减数分裂”有关。通过 PPI 网络分析后共选择了 20 个具有高程度的基因作为枢纽基因，其中包括丝裂原活化蛋白激酶 1（MAPK1）、MYC、早期生长反应 1（EGR1）、Bcl2 和钙调蛋白 1（CALM1）。通过 CCK8 实验、集落形成实验和划痕实验来验证京尼平的抗泌乳素瘤作用。流式细胞术的结果表明京尼平可增加细胞凋亡。筛选出 MAPK1、MYC、EGR1、Bcl2 和 CALM1 作为主要枢纽基因。京尼平上调 EGR1 和 p21（EGR1 的下游介质）和 EGR1 的表达水平，抑制泌乳素瘤细胞的增殖和迁移。京尼平是治疗泌乳素瘤患者的一种有前途的药物。
