Open Access

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

  • Authors:
    • Sheng Zhong
    • Bo Wu
    • Xinhui Wang
    • Dandan Sun
    • Daqun Liu
    • Shanshan Jiang
    • Junliang Ge
    • Yuan Zhang
    • Xinrui Liu
    • Xiaoli Zhou
    • Rihua Jin
    • Yong Chen
  • View Affiliations

  • Published online on: July 18, 2019     https://doi.org/10.3892/mmr.2019.10505
  • Pages: 2712-2724
  • Copyright: © Zhong et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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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.
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September 2019
Volume 20 Issue 3

Print ISSN: 1791-2997
Online ISSN:1791-3004

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Copy and paste a formatted citation
APA
Zhong, S., Wu, B., Wang, X., Sun, D., Liu, D., Jiang, S. ... Chen, Y. (2019). Identification of driver genes and key pathways of prolactinoma predicts the therapeutic effect of genipin. Molecular Medicine Reports, 20, 2712-2724. https://doi.org/10.3892/mmr.2019.10505
MLA
Zhong, S., Wu, B., Wang, X., Sun, D., Liu, D., Jiang, S., Ge, J., Zhang, Y., Liu, X., Zhou, X., Jin, R., Chen, Y."Identification of driver genes and key pathways of prolactinoma predicts the therapeutic effect of genipin". Molecular Medicine Reports 20.3 (2019): 2712-2724.
Chicago
Zhong, S., Wu, B., Wang, X., Sun, D., Liu, D., Jiang, S., Ge, J., Zhang, Y., Liu, X., Zhou, X., Jin, R., Chen, Y."Identification of driver genes and key pathways of prolactinoma predicts the therapeutic effect of genipin". Molecular Medicine Reports 20, no. 3 (2019): 2712-2724. https://doi.org/10.3892/mmr.2019.10505