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CCDC114, DNAI2 and TOP2A involves in the effects of tibolone treatment on postmenopausal endometrium

Yanhua Lv1, Yanqing Liu2, Yueqiang Wang3

  • 1Department of Gynecology, Affiliated Hospital of Jining Medical University, Jining, 272000, Shandong, China.

BMC Women'S Health
|June 12, 2021
PubMed
Abstract

Insights

Tibolone treatment in postmenopausal women impacts gene expression, particularly affecting cilium movement and hormone regulation. TOP2A emerged as a key drug target in endometrial tissue.

Area of Science:

  • Genomics
  • Molecular Biology
  • Pharmacology

Background:

  • Tibolone is a synthetic steroid used in hormone therapy for postmenopausal women.
  • Understanding its molecular mechanisms is crucial for optimizing treatment efficacy and safety.
  • Endometrial changes are a key consideration in tibolone therapy.

Purpose of the Study:

  • To elucidate the molecular mechanisms of tibolone action in postmenopausal women.
  • To identify key genes and pathways affected by tibolone treatment in the endometrium.
  • To predict potential drug targets for tibolone therapy.

Main Methods:

  • Analysis of gene expression data (GSE12446) from tibolone-treated and control endometrial samples.
  • Identification of differentially expressed genes (DEGs) and enrichment analysis for biological processes and pathways.
  • Construction of protein-protein interaction (PPI) networks and prediction of drug-gene interactions.

Main Results:

  • Identified 238 up-regulated and 72 down-regulated DEGs.
  • DEGs enriched in pathways including cilium movement, calcium ion homeostasis, and hormone level regulation.
  • Discovered significant drug-gene interactions, with TOP2A and HTR2B being targeted by multiple drugs, and TOP2A targeted by 7 known drugs.

Conclusions:

  • CCDC114 and DNAI2 may be important in tibolone's effects via cilium movement.
  • TOP2A is identified as a potential crucial target of tibolone in the postmenopausal endometrium.
  • This study provides insights into tibolone's molecular targets and pathways.
Keywords:
Differentially expressed genesFunction and pathway analysisGene–drug investigationPostmenopausal womenProtein–protein interaction network

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