Related Experiment Video
Updated: Dec 9, 2025

3-D Cell Culture System for Studying Invasion and Evaluating Therapeutics in Bladder Cancer
Published on: September 13, 2018
Phospholipase C-ε regulates bladder cancer cells via ATM/EXO1
Jiaxin Fan1, Yan Zhao1,2, Hongling Yuan1
1Key Laboratory of Diagnostics Medicine Designated by The Ministry of Education, Chongqing Medical University Chongqing, China.
Abstract:
Whole human genome microarray was performed to identify the potential molecular mechanisms associated with phospholipase C epsilon (PLCε). Gene Ontology, Kyoto Encyclopedia of Genes, and Genomes pathway analysis revealed that differentially expressed genes were significantly enriched in DNA repair-related pathways. Gene expression of PLCε, exonuclease 1 (EXO1), and ATM serine/threonine kinase (ATM) was significantly higher in 72 bladder cancer (BCa) tissue samples than in 24 samples of adjacent nonneoplastic tissue. The protein levels of PLCε and EXO1 showed appositive correlation in clinical bladder samples. Subsequent experiments showed that PLCε expression facilitated DNA repair in BCa by regulating ATM/EXO1 signaling. Additionally, we found that microRNA-145 is an antagonist of PLCε in T24 cells by directly targeting the 3'untranslated region of PLCε mRNA. Notably, microRNA-145 overexpression significantly increased the sensitivity to cisplatin, consistent with its PLCε silencing effect in BCa cells. Taken together, these findings reveal a novel physiological role for PLCε in DNA repair-related pathways with significant implications for the understanding of BCa biology.
Insights
Phospholipase C epsilon (PLCε) promotes DNA repair in bladder cancer (BCa) by regulating ATM/EXO1 signaling. MicroRNA-145 counteracts PLCε, enhancing cisplatin sensitivity in BCa cells.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Bladder cancer (BCa) involves complex molecular mechanisms.
- Understanding DNA repair pathways is crucial for BCa treatment.
- Phospholipase C epsilon (PLCε) role in BCa is not well-defined.
Purpose of the Study:
- To elucidate the molecular mechanisms of phospholipase C epsilon (PLCε) in bladder cancer (BCa).
- To investigate the role of PLCε in DNA repair pathways within BCa.
- To identify potential therapeutic targets for BCa treatment.
Main Methods:
- Whole human genome microarray analysis.
- Gene Ontology and KEGG pathway analysis.
- Quantitative gene expression and protein level analysis.
- In vitro studies involving microRNA manipulation.
Main Results:
- Differentially expressed genes in BCa were enriched in DNA repair pathways.
- PLCε, EXO1, and ATM gene expression were significantly upregulated in BCa tissues.
- PLCε expression positively correlated with EXO1 protein levels in BCa samples.
- PLCε facilitates DNA repair in BCa via ATM/EXO1 signaling.
- MicroRNA-145 acts as an antagonist to PLCε by targeting its mRNA.
- Overexpression of microRNA-145 enhanced cisplatin sensitivity in BCa cells.
Conclusions:
- PLCε plays a significant role in DNA repair pathways in bladder cancer.
- The PLCε/ATM/EXO1 signaling axis is a key regulator of DNA repair in BCa.
- MicroRNA-145 represents a potential therapeutic strategy to enhance BCa treatment efficacy, particularly with cisplatin.
More Related Videos
Related Concept Videos
Cancer Cell Migration through Invadopodia
Cell Motility through Blebbing
Blebbing Through the Matrix
In multicellular...
Intracellular Signaling Affects Focal Adhesions
Some...
Transducer Mechanism: Enzyme-Linked Receptors
Major types that are helpful drug targets include:
Membrane Asymmetry Regulating Transporters
Flippase
Eukaryotic flippases are type-IV P-type ATPases or P4-ATPases belonging to P-type ATPase family proteins that are membrane-bound pumps involved in the ATP-mediated transport of ions and molecules across the membrane. Flippases flip specific phospholipids from the outer to the inner leaflet of a membrane. All P4-ATPases have one...
Amplifying Signals via Enzymatic Cascade

