Cisplatin-based miRNA delivery strategy inspired by the circCPNE1/miR-330-3p pathway for oral squamous cell carcinoma

Area of Science:

• Oncology
• Molecular Biology
• Biomaterials

Background:

• Circular RNAs (circRNAs) are stable biomarkers for oral squamous cell carcinoma (OSCC) due to their structure.
• circRNAs function as microRNA (miRNA) sponges, influencing cancer progression.
• Dysregulated circRNAs are implicated in various cancers, including OSCC.

Purpose of the Study:

• To identify and characterize dysregulated circRNAs in OSCC.
• To investigate the role of circCPNE1 and miR-330-3p in OSCC.
• To develop a nanoparticle-based delivery system for miRNA inhibition in OSCC treatment.

Main Methods:

• Analysis of clinical OSCC samples to identify dysregulated circRNAs.
• Gain-of-function assays to determine the tumor-suppressive effect of circCPNE1.
• Design and synthesis of cationic polylysine-cisplatin prodrugs for antagomiR-330-3p delivery, forming PP@miR nanoparticles (NPs).

Main Results:

• circCPNE1 was identified as a dysregulated circRNA in OSCC, with lower expression correlating with advanced clinical stages.
• circCPNE1 acts as a sponge for miR-330-3p, a tumor promoter that enhances OSCC cell proliferation, migration, and invasion.
• PP@miR NPs effectively inhibited subcutaneous OSCC tumor growth and led to partial tumor elimination in vivo.

Conclusions:

• circCPNE1 exhibits tumor-suppressive properties in OSCC.
• Selective inhibition of the oncogenic miR-330-3p is a viable strategy for OSCC treatment.
• The developed PP@miR nanoparticle system demonstrates potential for targeted miRNA-based therapy in OSCC.