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中国癌症防治杂志

中国癌症防治杂志 ›› 2025, Vol. 17 ›› Issue (4): 473-482.doi: 10.3969/j.issn.1674-5671.2025.04.12

• 论著 • 上一篇    下一篇

miR⁃145⁃3p靶向MTDH抑制鼻咽癌细胞侵袭及血管生成

  

  1. 广西医科大学附属肿瘤医院放疗科；广西医科大学附属武鸣医院肿瘤科
  • 出版日期:2025-08-25 发布日期:2025-09-12
  • 通讯作者: 朱小东 E-mail：zhuxdonggxmu@126.com
  • 基金资助:
    广西重点研发计划项目 (桂科AB23026020)；广西自然科学基金区域高发疾病研究联合专项资助项目（2023GXNSFBA026012）；广西高校中青年教师科研基础能力提升项目（2022KY0087）

miR⁃145⁃3p inhibits the invasion and angiogenesis of nasopharyngeal carcinoma cells through the targeting MTDH

  • Online:2025-08-25 Published:2025-09-12

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摘要： 目的 探讨miR⁃145⁃3p对鼻咽癌细胞迁移、侵袭及血管生成的调控作用及其分子机制。 方法 利用miR⁃145⁃3p抑制剂/模拟物和相应对照RNA 寡核苷酸，以及慢病毒载体，构建miR⁃145⁃3p表达被抑制/上调表达的鼻咽癌细胞系CNE⁃2和5⁃8F。采用实时荧光定量PCR（quantitative reverse transcription PCR，RT⁃qPCR）检测miR⁃145⁃3p和异黏蛋白（metadherin,MTDH）的相对表达量。通过划痕实验、Transwell小室迁移/侵袭实验及血管形成实验评估miR⁃145⁃3p表达对鼻咽癌细胞迁移、侵袭和血管生成的影响。利用生物信息学工具预测miR⁃145⁃3p的潜在靶基因，并通过双荧光素酶报告基因系统、RT⁃qPCR及Western blot验证miR⁃145⁃3p与MTDH的相互作用。此外， Western blot检测miR⁃145⁃3p对上皮⁃间质转化相关蛋白（E⁃cadherin和N⁃cadherin）、侵袭与血管生成相关蛋白（MMP9）、自噬相关蛋白（LC3B）及AKT/mTOR信号通路相关蛋白（p⁃AKT和p⁃mTOR）表达的影响。 结果 miR⁃145⁃3p在鼻咽癌细胞中低表达（P<0.05）。上调miR⁃145⁃3p表达可显著抑制鼻咽癌细胞迁移、侵袭及血管生成（均P<0.05）。此外，这种上调导致E⁃cadherin表达增加， LC3B Ⅱ/LC3B Ⅰ比值升高（均P<0.05），下调N⁃cadherin、MMP9、p⁃AKT和p⁃mTOR的表达（均P<0.05）；而抑制miR⁃145⁃3p表达则产生相反效果。miR⁃145⁃3p可靶向负调控MTDH表达（P<0.05）。 结论 miR⁃145⁃3p通过靶向MTDH抑制AKT/mTOR信号通路，在鼻咽癌中促进自噬，从而抑制上皮⁃间质转化及血管生成。

关键词: 鼻咽癌, miR-145-3p, 自噬, 上皮-间质转化, 侵袭, 血管生成

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

中图分类号: 

  • R739.63