Department of Physical Medicine and Rehabilitation, Chung Shan Medical University Hospital, Taichung, Taiwan.
Biochem Biophys Res Commun. 2012 Aug 24;425(2):462-7. doi: 10.1016/j.bbrc.2012.07.125. Epub 2012 Jul 27.
Myeloid zinc finger 1 (MZF1) gene belongs to the Kruppel family of zinc finger transcription factors. MZF1 has been suggested to play an important role in the tumorigenesis, invasion, and apoptosis of various tumor cells. However, the role of MZF1 in human cervical cancer remains unclear. To investigate the molecular mechanisms of MZF1 and its functional role in human cervical cancer cell migration and invasion, we experimented on stable SiHa cells overexpressing MZF1. We found that MZF1 overexpression inhibits the migratory and invasive abilities of SiHa cervical cancer cells. In addition, the overexpression of MZF1 significantly reduces MMP-2 protein and mRNA levels. Luciferase and ChIP assays suggested that MZF1 directly binds to MMP-2 gene regulatory sequences in vivo and suppresses MMP-2 promoter activity in vitro. This study shows that MZF-1 represses MMP-2 transcription and suggests that this repression may be linked to inhibition of human cervical cancer cell migration and metastasis.
髓样锌指蛋白 1（MZF1）基因属于锌指转录因子的 Kruppel 家族。已有研究表明，MZF1 在多种肿瘤细胞的肿瘤发生、侵袭和凋亡中发挥重要作用。然而，MZF1 在人宫颈癌中的作用尚不清楚。为了研究 MZF1 的分子机制及其在人宫颈癌细胞迁移和侵袭中的功能作用，我们在稳定过表达 MZF1 的 SiHa 细胞上进行了实验。我们发现，MZF1 的过表达抑制了 SiHa 宫颈癌细胞的迁移和侵袭能力。此外，MZF1 的过表达显著降低了 MMP-2 蛋白和 mRNA 水平。荧光素酶和 ChIP 实验表明，MZF1 可在体内直接结合 MMP-2 基因调控序列，并在体外抑制 MMP-2 启动子活性。本研究表明 MZF-1 抑制 MMP-2 的转录，并提示这种抑制可能与抑制人宫颈癌细胞的迁移和转移有关。
