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Published on: December 1, 2013
A miR-124-3p/PKC-δ Regulatory Axis Restrains Bladder Cancer Growth and Malignant Progression
Yu-Cheng Kuo1,2, Hsiao-Yu Wang3, Tsai-Lan Liao4
1School of Medicine, College of Medicine, China Medical University, Taichung, Taiwan, R.O.C.
Background/Aim:
Bladder cancer is characterized by high rates of recurrence and metastasis, underscoring the need for novel molecular targets. Protein kinase C delta (PKC-δ) has been implicated in tumor progression, yet its regulatory mechanisms in bladder cancer remain unclear. MicroRNAs (miRNAs) function as crucial post-transcriptional regulators, and miR-124-3p is recognized as a potent tumor suppressor that inhibits oncogenic signaling across various malignancies. However, its specific interaction with PKC-δ in bladder cancer has not been established. This study aimed to investigate the regulatory role of the miR-124-3p/PKC-δ axis in modulating the malignant phenotypes of bladder cancer cells.
Materials And Methods:
Human bladder cancer cell lines TSGH8301 and T24 were treated with the PKC inhibitor rottlerin or transfected with miR-124-3p mimic. Cell viability, proliferation, migration, invasion, epithelial-mesenchymal transition (EMT), and stemness were evaluated using cytotoxicity assays, Transwell assays, sphere formation assays, flow cytometry, and western blotting.
Results:
Rottlerin suppressed bladder cancer cell proliferation and upregulated miR-124-3p expression. Overexpression of miR-124-3p reduced PKC-δ expression and phosphorylation, inhibited migration, invasion, EMT, and stemness, and phenocopied the effects of PKC inhibition.
Conclusion:
miR-124-3p negatively regulates PKC-δ signaling in bladder cancer cells, forming a novel miR-124-3p/PKC-δ axis that suppresses bladder cancer progression and may offer therapeutic value.
Insights
MicroRNA-124-3p suppresses bladder cancer progression by targeting Protein Kinase C delta (PKC-δ). This novel axis inhibits cell migration, invasion, and stemness, offering potential therapeutic strategies for bladder cancer.
Area of Science:
- Oncology
- Molecular Biology
- Gene Regulation
Background:
- Bladder cancer exhibits high recurrence and metastasis rates, necessitating new molecular targets.
- Protein kinase C delta (PKC-δ) is implicated in tumor progression, but its regulation in bladder cancer is unclear.
- MicroRNAs (miRNAs) are key regulators; miR-124-3p acts as a tumor suppressor, but its role with PKC-δ in bladder cancer is unestablished.
Purpose of the Study:
- To investigate the regulatory role of the miR-124-3p/PKC-δ axis.
- To determine the impact of this axis on bladder cancer cell malignant phenotypes.
Main Methods:
- Utilized human bladder cancer cell lines (TSGH8301, T24).
- Administered PKC inhibitor rottlerin and transfected with miR-124-3p mimic.
- Assessed cell viability, proliferation, migration, invasion, epithelial-mesenchymal transition (EMT), and stemness via various assays and western blotting.
Main Results:
- PKC inhibition (rottlerin) suppressed proliferation and increased miR-124-3p expression.
- miR-124-3p overexpression reduced PKC-δ expression and phosphorylation.
- Overexpression of miR-124-3p inhibited migration, invasion, EMT, and stemness, mimicking PKC inhibition effects.
Conclusions:
- A novel miR-124-3p/PKC-δ axis negatively regulates PKC-δ signaling in bladder cancer.
- This axis suppresses bladder cancer progression, indicating potential therapeutic value.
