MTP18在口腔鳞癌细胞迁移与侵袭中的作用

  目的  探讨线粒体蛋白18(mitochondrial protein 18，MTP18)在口腔鳞癌转移中的调控作用。  方法  (1) 采用生物信息分析44例正常口腔黏膜与520例口腔鳞癌组织中MTP18的表达。(2)siRNA干涉MTP18表达后，用qRT-PCR与Western blotting实验检测干涉效果，用划痕与Transwell实验检测对细胞迁移与侵袭能力的影响。(3)siRNA下调MTP18表达后，用qRT-PCR实验分析对细胞上皮间质转化的影响。  结果  (1) 口腔鳞癌中MTP18表达显著上调(P＜0.001)，尤其在高级别与淋巴转移的肿瘤组织中。(2)siRNA显著下调了MTP18表达(P＜0.001)。干涉MTP18可显著抑制口腔鳞癌SCC9细胞的迁移(siCtrl vs.siMTP18#1 vs. siMTP18#2为1.00±0.07 vs. 0.43±0.04 vs. 0.44±0.03，F=102.241, P＜0.001)与侵袭(siCtrl vs. siMTP18#1 vs. siMTP18#2为1.00±0.07 vs. 0.43±0.04 vs. 0.44±0.03，F=97.017, P＜0.001)。(3)干涉MTP18上调了上皮细胞标志分子的表达(P＜0.001)，而下调了间质细胞标志分子的表达(P＜0.001)。  结论  MTP18通过诱导上皮间质转化促进口腔鳞癌细胞的迁移与侵袭。 

MTP18 promotes oral squamous-cell carcinoma metastasis through induction of epithelial-mesenchymal transition

  Objective  To explore the biological functions of mitochondrial protein 18 (MTP18) in oral squamous-cell carcinoma metastasis.  Methods  (1) Bioinformatic analysis was conducted to evaluate the expression of MTP18 in 44 normal oral mucosa and 520 oral squamous-cell carcinoma tissues. (2) The silencing effect of MTP18 by siRNA was measured by qRT-PCR and Western blot analysis. In addition, the effects of MTP18 knockdown on the migration and invasion abilities of oral squamous-cell carcinoma were determined by wound-healing and Transwell invasion assays. (3) The effects of MTP18 knockdown on the expressions of markers in epithelial-mesenchymal transition (EMT) were determined by qRT-PCR analysis.  Results  (1) Bioinformatic analysis indicated that MTP18 expression was significantly increased in tumour tissues of oral squamous-cell carcinoma, especially in tumour tissues at high stages and with lymph node metastasis, compared with normal tissues (P < 0.001). (2) siRNA transfection successfully reduced the expression of MTP18 in oral squamous-cell carcinoma cells (P < 0.001). MTP18 knockdown significantly suppressed cell migration (siCtrl vs. siMTP18#1 vs. siMTP18#2: 1.00±0.07 vs. 0.43±0.04 vs. 0.44±0.03, F=102.241, P < 0.001) and invasion (siCtrl vs. siMTP18#1 vs. siMTP18#2: 1.00±0.07 vs. 0.43±0.04 vs. 0.44±0.03, F=97.017, P < 0.001). (3) MTP18 knockdown significantly increased the expressions of epithelial cell markers (P < 0.001), but suppressed the expressions of mesenchymal cell markers (P < 0.001).  Conclusion  MTP18 overexpression promotes oral squamous-cell carcinoma metastasis mainly through the induction of EMT.