From miRNA Sponges to mTOR Blockades: Mapping the Multidimensional Landscape of Ameloblastoma Pathogenesis and Precision Targeting

Jingsong MaoQingxuan GaiXinling BaoMing Zhong^*

• School of Stomatology, China Medical University, Shenyang, China

Although histologically benign, an odontogenic tumor known as ameloblastoma exhibits considerable potential to recur after surgery and aggressive local invasion. Over the past 10 years, frag-mented molecular research has come together around a uniting theme: dysregulated non coding RNA circuitry; mostly microRNAs (miRNAs) and circular RNAs (circRNAs) acts as a molecular "switchboard" re wiring basic carcinogenic routes. Combining the most significant primary results released by May 2025, this narrative review produces a convincing picture of those relationships and their therapeutic effects. Important oncogenic drivers are miR-29a-3p, which promotes Wnt/β-catenin signaling to boost migration and invasion, and circRNAs that sequesters tumor-suppressive miRNAs, hence retaining constitutive activation of MAPK and PI3K/Akt/mTOR cascade. Loss-of-function events in miR-524-5p, miR-141-3p and miR-1-3p remove brakes on tumors promoting axis IL-33/ST2, NCAM1, and LAMP2-mediated autophagy. These ncRNA pathway loops taken together support proliferation, epithelial– mesenchymal transition, angiogenesis, and resistance against death—molecular markers reflecting the clinical behavior of the malignancy. Pre-clinical studies demonstrate that pharmacologic suppression of Akt/mTOR or dual inhibition of PI3K/mTOR inhibits growth in ameloblastoma organoids and xenografts especially when paired with BRAF/MAPK inhibitors. Emerging delivery systems— nanoparticle-encapsulated miRNA mimics/inhibitors offer additional precise points even though they remain in an early translational stage. Combining several results, this review emphasizes two main messages: (i) ameloblastoma pathogenesis is orchestrated by a multidimensional ncRNA network converging on druggable signalling nodes; and (ii) future progress depends on multicentre biobanking for robust ncRNA biomarker validation, rational combination therapies that flank Akt/mTOR with MAPK blockade, and tumor targeted delivery systems minimising surgical morbidity. Thus, a greater molecular knowledge has significant potential to transform ameloblastoma treatment from primarily surgical to actually precision-guided treatment.