首页|Cisplatin-based miRNA delivery strategy inspired by the circCPNE1/miR-330-3p pathway for oral squamous cell carcinoma
Cisplatin-based miRNA delivery strategy inspired by the circCPNE1/miR-330-3p pathway for oral squamous cell carcinoma
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Circular RNAs(circRNAs)are ideal biomarkers of oral squamous cell carcinoma(OSCC)because of their highly stable closed-loop structure,and they can act as microRNA(miRNA)sponges to regulate OSCC progression.By analyzing clinical samples,we identified circCPNEl,a dysregulated circRNA in OSCC,and its expression level was negatively correlated with the clinical stage of OSCC patients.Gain-of-function assays revealed the tumor-suppressive effect of circCPNE1,which was then identified as a miR-330-3p sponge.MiR-330-3p was recognized as a tumor promoter in multiple studies,consistent with our finding that it could promote the proliferation,migration,and invasion of OSCC cells.These results indicated that selective inhibition of miR-330-3p could be an effective strategy to inhibit OSCC progression.Therefore,we designed cationic polylysine-cisplatin prodrugs to deliver antago-miR-330-3p(a miRNA inhibitory analog)via electrostatic interactions to form PP@miR nanoparticles(NPs).Paratumoral administration results revealed that PP@miR NPs effectively inhibited subcutaneous tumor progression and achieved partial tumor elimination(2/5),which confirmed the critical role of miR-330-3p in OSCC development.These findings provide a new perspective for the development of OSCC treatments.
Hua-yang Fan、Ming-da Zhao、Hong-jie Jiang、Zhen-wei Yu、Yu-jiang Fan、Xin-hua Liang、Ya-ling Tang、Yong Sun
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State Key Laboratory of Oral Diseases & National Center for Stomatology & National Clinical Research Center for Oral Diseases & Department of Oral and Maxillofacial Surgery,West China Hospital of Stomatology,Sichuan University,Chengdu 610041,China
National Engineering Research Center for Biomaterials,Sichuan University,Chengdu 610065,China
State Key Laboratory of Oral Diseases & National Center for Stomatology & National Clinical Research Center for Oral Diseases & Department of Oral Pathology,West China Hospital of Stomatology,Sichuan University,Chengdu 610041,China
National Natural Science Foundation of ChinaNational Natural Science Foundation of ChinaNational Natural Science Foundation of ChinaNational Natural Science Foundation of ChinaScience Foundation of Sichuan Province,ChinaInterdisciplinary innovation project of West China College of Stomatology,Sichuan University,China
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