Related Experiment Video
Updated: Sep 5, 2025
Studying TGF-β Signaling and TGF-β-induced Epithelial-to-mesenchymal Transition in Breast Cancer and Normal Cells
Published on: October 27, 2020
Blocking ATM Attenuates SKOV3 Cell Proliferation and Migration by Disturbing OGT/OGA Expression via hsa-miR-542-5p
Ning Wang1,2, Miaomiao Yu1,3, Yan Fu4
1Central Laboratory, The First Hospital of Jilin University, Changchun, China.
Abstract:
Blocking ataxia telangiectasia mutated (ATM), a crucial player in DNA repair responses, has been proposed as a promising strategy in anti-cancer therapy. Most previous studies have focused on DNA damage response-related pathways after administration of ATM inhibitors. However, ATM inhibition could potentially influence a wide range of changes in gene expression, which remain poorly defined. Here, we report that administration of the ATM inhibitor KU60019 led to impaired migration and enhanced apoptosis in the ovarian cancer cell line SKOV3, accompanied by abnormally elevated O-GlcNAc transferase and O-GlcNAcase expression levels. In addition, KU60019 treatment significantly suppressed expression of hsa-miR-542-5p in SKOV3 cells. Up-regulation of hsa-miR-542-5p expression inhibited increases in OGT and OGA level, and reversed the effects of ATM inhibition on apoptosis and migration in SKOV3 cells. Finally, we found aberrant expression of OGT and OGA to be associated with ovarian cancer patient survival. Taken together, our results suggest that ATM inhibition may promote SKOV3 cell apoptosis via suppressing hsa-miR-542-5p and elevating OGT and OGA expression, providing new insights into the application of ATM inhibitors in cancer immunotherapy.
Insights
Blocking ataxia telangiectasia mutated (ATM) inhibitors enhance ovarian cancer cell death and impair migration. This occurs via suppressing hsa-miR-542-5p and elevating O-GlcNAc transferase (OGT) and O-GlcNAcase (OGA) expression, offering new cancer immunotherapy insights.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- Ataxia telangiectasia mutated (ATM) is vital for DNA repair and a target for anti-cancer therapy.
- Previous research focused on DNA damage pathways, but ATM inhibition's broader gene expression effects are unclear.
Purpose of the Study:
- To investigate the effects of ATM inhibition on ovarian cancer cell behavior and gene expression.
- To explore the role of O-GlcNAcylation and microRNAs in ATM-inhibited ovarian cancer.
Main Methods:
- Utilized the ATM inhibitor KU60019 on the SKOV3 ovarian cancer cell line.
- Monitored cell apoptosis, migration, and expression levels of O-GlcNAc transferase (OGT), O-GlcNAcase (OGA), and hsa-miR-542-5p.
- Assessed the impact of hsa-miR-542-5p up-regulation on cellular responses.
Main Results:
- KU60019 treatment impaired SKOV3 cell migration and enhanced apoptosis.
- ATM inhibition led to increased OGT and OGA expression and decreased hsa-miR-542-5p levels.
- Restoring hsa-miR-542-5p suppressed OGT/OGA elevation and reversed KU60019's effects on apoptosis and migration.
- Aberrant OGT and OGA expression correlated with ovarian cancer patient survival.
Conclusions:
- ATM inhibition promotes ovarian cancer cell apoptosis by suppressing hsa-miR-542-5p and elevating OGT and OGA.
- This mechanism offers novel insights into applying ATM inhibitors in cancer immunotherapy.
- OGT and OGA represent potential therapeutic targets in ovarian cancer.
