Abstract
Sinonasal inverted papilloma (SNIP) is a benign epithelial neoplasm of the Schneiderian membrane, known for its locally aggressive behavior, high recurrence rates, and potential for malignant transformation into sinonasal squamous cell carcinoma (SNSCC). Emerging evidence emphasizes the role of microRNAs (miRNAs) in the pathogenesis, progression, and clinical management of SNIP. These small non-coding RNAs regulate key cellular pathways, particularly the PTEN/PI3K/AKT axis, which governs tumor growth, apoptosis resistance, and chemoresistance. Among the miRNAs studied, miR-296-3p, miR-214-3p, and the miR-449 cluster show significant dysregulation. miR-296-3p is upregulated in SNSCC, promoting oncogenesis by inhibiting PTEN and activating the PI3K/Akt pathway. Conversely, miR-214-3p is downregulated in SNIP and correlates with advanced disease and increased recurrence, identifying it as a potential diagnostic and prognostic biomarker. The miR-449 cluster, with known tumor-suppressive properties, is progressively downregulated during malignant transformation, highlighting its role in maintaining epithelial structure. Despite their promise, clinical application of miRNA-based diagnostics and therapies faces challenges such as delivery optimization, specificity, and off-target effects. Nonetheless, the noninvasive detection of circulating miRNAs in bodily fluids offers a compelling approach for future diagnostic tools and patient monitoring. This review highlights the transformative potential of miRNA research in advancing SNIP diagnosis and treatment. By integrating molecular insights into clinical practice, miRNA-based strategies could pave the way for more personalized interventions, ultimately reducing recurrence rates and preventing malignant transformation.