Wang Bin, Lv Kexing, Chen Weixiong, Zhao Jing, Luo Jie, Wu Jianhui, Li Zenghong, Qin Hao, Wong Thian-Sze, Yang Weiqiang, Fu Qing-Ling, Lei Wenbin
Department of Otorhinolaryngology, The First Affiliated Hospital of Sun Yat-Sen University, Otorhinolaryngology Institute, Sun Yat-Sen University, Guangzhou, China.
Department of Otorhinolaryngology, The First People's Hospital of Foshan, Foshan, China.
Biomed Res Int. 2016;2016:9652789. doi: 10.1155/2016/9652789. Epub 2016 Dec 19.
Previous studies have found that miR-375 and miR-205 were significantly dysregulated in laryngeal squamous cell carcinoma, which contributed to the invasion and migration of LSCC. However, the mechanisms of miR-375 and miR-205 regulating the invasion and migration of LSCC remain unknown. qRT-PCR was performed in 40 pairs of tissue samples to investigate the expression of miR-375 and miR-205 in LSCC and paracarcinoma tissues. To investigate whether or not miR-375 and miR-205 regulated the invasion and migration of LSCC synergistically via AKT-mediated epithelial-mesenchymal transition, miR-375 mimic and miR-205 inhibitor were transfected into SNU899 cells and miR-375 inhibitor and miR-205 mimic were transfected into SNU899 cells, respectively, with or without AKT inhibitor. Then the expressions of miR-375 and miR-205 were validated by qRT-PCR, cell migration and invasion were determined by wound healing assay and transwell invasive assay, and western blot analysis was performed to detect the expression of related proteins. Our results showed that miR-375 and miR-205 regulated the invasion and migration of LSCC via AKT-mediated EMT synergistically. In conclusion, our findings provided not only new information about the molecular mechanism of miRNAs regulating invasion and migration of LSCC, but also a theoretical principle for potential targeting therapy of laryngeal squamous carcinoma.
以往研究发现,miR-375和miR-205在喉鳞状细胞癌中显著失调,这促进了喉鳞状细胞癌的侵袭和迁移。然而,miR-375和miR-205调控喉鳞状细胞癌侵袭和迁移的机制仍不清楚。对40对组织样本进行qRT-PCR,以研究miR-375和miR-205在喉鳞状细胞癌组织和癌旁组织中的表达。为了研究miR-375和miR-205是否通过AKT介导的上皮-间质转化协同调控喉鳞状细胞癌的侵袭和迁移,将miR-375模拟物和miR-205抑制剂分别转染至SNU899细胞中,以及将miR-375抑制剂和miR-205模拟物分别转染至SNU899细胞中,同时加入或不加入AKT抑制剂。然后通过qRT-PCR验证miR-375和miR-205的表达,通过伤口愈合试验和Transwell侵袭试验测定细胞迁移和侵袭能力,并进行蛋白质印迹分析以检测相关蛋白的表达。我们的结果表明,miR-375和miR-205通过AKT介导的EMT协同调控喉鳞状细胞癌的侵袭和迁移。总之,我们的研究结果不仅提供了有关miRNAs调控喉鳞状细胞癌侵袭和迁移分子机制的新信息,也为喉鳞状细胞癌潜在的靶向治疗提供了理论依据。