Abstract: Objective To investigate the regulatory function of miR⁃145⁃3p in the processes of migration， invasion， and angiogenesis in nasopharyngeal carcinoma cells， as well as to explore the underlying molecular mechanisms. Methods Nasopharyngeal carcinoma cell lines CNE⁃2 and 5⁃8F were engineered to exhibit either suppressed or enhanced expression of miR⁃145⁃3p through the use of miR⁃145⁃3p inhibitors/mimics and corresponding control RNA oligos， as well as lentiviral vectors. Quantitative reverse transcription PCR (RT⁃qPCR) was employed to assess the relative expression levels of miR⁃145⁃3p and metadherin (MTDH). The impact of miR⁃145⁃3p expression on cellular migration， invasion， and angiogenesis was evaluated using wound healing assays， Transwell migration/invasion assays， and tube formation assays. Bioinformatics tools were utilized to predict potential target genes of miR⁃145⁃3p， the interaction between miR⁃145⁃3p and MTDH was validated through dual luciferase reporter assays， RT⁃qPCR， and Western blot analysis. Additionally， Western blotting was conducted to examine the influence of miR⁃145⁃3p on the expression of proteins associated with epithelial mesenchymal transition (E⁃cadherin and N⁃cadherin)， invasion and angiogenesis (MMP9)， autophagy (LC3B)， and AKT/mTOR signaling pathway (p⁃AKT and p⁃mTOR). Results In nasopharyngeal carcinoma cells， miR⁃145⁃3p was found to be expressed at low levels (P<0.05). Enhancement of miR⁃145⁃3p expression was associated with significant inhibition of cell migration， invasion， and angiogenesis (all P<0.05). Furthermore， this upregulation led to increased expression of E⁃cadherin and an elevated LC3BⅡ/LC3B I ratio (all P<0.05)， and while concurrently reducing the expression of levels N⁃cadherin， MMP9， p⁃AKT and p⁃mTOR (all P<0.05). Conversely， suppression of miR⁃145⁃3p expression yielded opposite outcomes. miR⁃145⁃3p was also demonstrated to target MTDH， thereby negatively regulating its expression (P<0.05). Conclusions miR⁃145⁃3p inhibits the AKT/mTOR signaling pathway by targeting MTDH in nasopharyngeal carcinoma， which in turn promotes autophagy and exerts inhibitory effects on epithelial⁃mesenchymal transition and angiogenesis.

Key words: Nasopharyngeal carcinoma, miR-145-3p, Autophagy, Epithelial-mesenchymal transition, Invasion, Angiogenesis