PDF(Pubmed)
Abstract：
Zinc finger MIZ-type containing 1 (ZMIZ1) is a transcriptional coactivator related to the protein inhibitors of activated STATs (PIAS) family. Mounting evidence suggests that ZMIZ1 plays a crucial role in the occurrence and development of cancers. The function of ZMIZ1 in tongue squamous cell carcinoma (TSCC) and the mechanisms underpinning its role in this disease have not been fully clarified. We performed qualitative ZMIZ1 protein expression analyses using immunohistochemistry in 20 patient-derived, paraffin-embedded TSCC tissue sections. We used RNAi to knock down ZMIZ1 expression in the CAL-27 TSCC cell line and quantified the impact of ZMIZ1 knock down on proliferation, migration and apoptosis via CCK-8, scratch assay and flow cytometry, respectively. We used qRT-PCR and western blotting to investigate the role of ZMIZ1 in this cell line. Finally, we established a model of lung metastasis in nude mice to replicate the in vitro results. ZMIZ1 protein was significantly more abundant in TSCC case tissue samples. ZMIZ1 knockdown reduced the invasion and metastases of TSCC tumor cells and promoted apoptosis. ZMIZ1 knockdown was associated with the down-regulation of Notch signaling pathway related factors Jagged1 and Notch1, and invasion and metastasis related factors MKP-1, SSBP2 and MMP7 in vitro and in vivo, at the mRNA level. In vitro and in vivo data suggest that knock down of ZMIZ1 may inhibit TSCC invasion and metastasis by modulating Notch signaling. ZMIZ1 inhibition may therefore represent a new therapeutic target for TSCC.
摘要：
含锌指MIZ型1(ZMIZ1)是与激活的STATs(PIAS)家族的蛋白质抑制剂相关的转录共激活因子。越来越多的证据表明，ZMIZ1在癌症的发生和发展中起着至关重要的作用。ZMIZ1在舌鳞状细胞癌（TSCC）中的功能及其在该疾病中的作用机制尚未完全阐明。我们使用免疫组织化学对20名患者来源的ZMIZ1蛋白表达进行了定性分析，石蜡包埋的TSCC组织切片。我们使用RNAi在CAL-27TSCC细胞系中敲低ZMIZ1表达，并定量ZMIZ1敲低对增殖的影响，通过CCK-8，划痕分析和流式细胞术，分别。我们使用qRT-PCR和蛋白质印迹来研究ZMIZ1在该细胞系中的作用。最后,我们建立了裸鼠肺转移模型，以复制体外结果。ZMIZ1蛋白在TSCC病例组织样品中明显更丰富。ZMIZ1敲低可降低TSCC肿瘤细胞的侵袭和转移，促进细胞凋亡。ZMIZ1敲低与Notch信号通路相关因子Jagged1和Notch1、侵袭转移相关因子MKP-1、SSBP2和MMP7的表达下调有关,在mRNA水平。体外和体内数据表明，敲低ZMIZ1可能通过调节Notch信号传导来抑制TSCC的侵袭和转移。因此,ZMIZ1抑制可以代表TSCC的新治疗靶标。
