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 circCPNE1, 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 antagomiR-330–3p (a miRNA inhibitory analog) 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.

中文翻译：

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受口腔鳞状细胞癌 circCPNE1/miR-330-3p 通路启发的基于顺铂的 miRNA 递送策略

环状RNA（circRNA）因其高度稳定的闭环结构而成为口腔鳞状细胞癌（OSCC）的理想生物标志物，并且它们可以作为微小RNA（miRNA）海绵来调节OSCC的进展。通过分析临床样本，我们发现了 circCPNE1，一种在 OSCC 中失调的 circRNA，其表达水平与 OSCC 患者的临床分期呈负相关。功能获得分析揭示了 circCPNE1 的肿瘤抑制作用，随后将其鉴定为 miR-330–3p 海绵。MiR-330-3p在多项研究中被认为是肿瘤促进剂，这与我们的发现一致，即它可以促进OSCC细胞的增殖、迁移和侵袭。这些结果表明，选择性抑制 miR-330-3p 可能是抑制 OSCC 进展的有效策略。因此，我们设计了阳离子聚赖氨酸-顺铂前药来传递 antagomiR-330–3p（一种 miRNA 抑制类似物）静电相互作用，形成 PP@miR 纳米颗粒（NP）。瘤旁给药结果显示，PP@miR NPs 有效抑制皮下肿瘤进展并实现部分肿瘤消除（2/5），这证实了 miR-330–3p 在 OSCC 发展中的关键作用。这些发现为口腔鳞癌治疗的发展提供了新的视角。