Lan Ying, Zhao Shijie, Hou Tao, Ren Yi, Tang Jun, Yin Shihua, Wu Yang
Department of Otolaryngology Head and Neck Surgery, The Third Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, China.
Department of Otolaryngology Head and Neck Surgery, The Second Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, China.
Heliyon. 2024 Nov 28;10(23):e40760. doi: 10.1016/j.heliyon.2024.e40760. eCollection 2024 Dec 15.
To explore the mechanism of HIF-1α promoting the proliferation, invasion and metastasis of nasopharyngeal carcinoma cells by regulating the expression of MMP-2.
30 nasopharyngeal carcinoma tissues and 30 normal nasopharyngeal epithelial tissues were collected, and the expression of HIF-1α and MMP-2 in the nasopharyngeal carcinoma, normal nasopharyngeal epithelial tissues and their hypoxic environment were systematically analyzed by qRT-PCR and western blot techniques. Lentivirus transfection technology was used to regulate the expression of HIF-1α and MMP-2 genes in the HONE1 cell line under hypoxic environment, and to explore the interaction mechanism of HIF-1α and MMP-2 genes and their role in the proliferation, invasion and metastasis of nasopharyngeal carcinoma. Furthermore, the cytological behavior changes regulated by HIF-1α and MMP-2 genes were further explored by gene chip technology.
The expressions of HIF-1α and MMP-2 in nasopharyngeal carcinoma tissues were significantly higher than those in normal nasopharyngeal epithelial tissues (P < 0.05). Compared with normoxic group, the expression of HIF-1α and MMP-2 in the nasopharyngeal carcinoma cell line HONE1 increased in hypoxic group (P < 0.05). Compared with NC-siRNA group, the expression of HIF-1α in si-HIF-1α group decreased, and the cell proliferation ability and invasion and metastasis ability decreased (P < 0.05). PCR array analysis revealed that the mRNA expressions of FAS, BRCA1, TIMP-1 genes were up-regulated in nasopharyngeal carcinoma HONE1 cells with HIF-1α gene silencing. AKT1, VEGFA, MET, MMP-2, MMP-9 and MTA2 were down-regulated. Compared with NC-siRNA group, the expression of MMP-2 in si-MMP-2 group decreased, and the ability of cell proliferation and invasion and metastasis decreased (P < 0.05).
HIF-1α could inhibit the proliferation, invasion and metastasis of nasopharyngeal carcinoma by regulating the expression of MMP-2, thus inhibiting tumor growth. Therefore, HIF-1α and MMP-2 might become important therapeutic targets to inhibit the growth, invasion and metastasis of nasopharyngeal carcinoma.
探讨缺氧诱导因子-1α（HIF-1α）通过调节基质金属蛋白酶-2（MMP-2）的表达促进鼻咽癌细胞增殖、侵袭和转移的机制。
收集30例鼻咽癌组织和30例正常鼻咽上皮组织，采用qRT-PCR和蛋白质印迹技术系统分析HIF-1α和MMP-2在鼻咽癌组织、正常鼻咽上皮组织及其缺氧环境中的表达。利用慢病毒转染技术在缺氧环境下调节HONE1细胞系中HIF-1α和MMP-2基因的表达，探讨HIF-1α与MMP-2基因的相互作用机制及其在鼻咽癌细胞增殖、侵袭和转移中的作用。此外，通过基因芯片技术进一步探索HIF-1α和MMP-2基因调控的细胞学行为变化。
鼻咽癌组织中HIF-1α和MMP-2的表达明显高于正常鼻咽上皮组织（P<0.05）。与常氧组相比，鼻咽癌细胞系HONE1在缺氧组中HIF-1α和MMP-2的表达增加（P<0.05）。与阴性对照小干扰RNA（NC-siRNA）组相比，小干扰RNA-HIF-1α（si-HIF-1α）组中HIF-1α的表达降低，细胞增殖能力以及侵袭和转移能力降低（P<0.05）。PCR芯片分析显示，在HIF-1α基因沉默的鼻咽癌HONE1细胞中，FAS、BRCA1、TIMP-1基因的信使核糖核酸（mRNA）表达上调。AKT1、VEGFA、MET、MMP-2、MMP-9和MTA2表达下调。与NC-siRNA组相比，小干扰RNA-MMP-2（si-MMP-2）组中MMP-2的表达降低，细胞增殖以及侵袭和转移能力降低（P<0.05）。
HIF-1α可通过调节MMP-2的表达抑制鼻咽癌细胞的增殖、侵袭和转移，从而抑制肿瘤生长。因此，HIF-1α和MMP-2可能成为抑制鼻咽癌生长、侵袭和转移的重要治疗靶点。
