A miR-124-3p/PKC-δ Regulatory Axis Restrains Bladder Cancer Growth and Malignant Progression

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.