Department of chest surgery, The second affiliated hospital of Air Force Military medical University, Xi'an, Shanxi, China.
Anticancer Drugs. 2020 Mar;31(3):282-291. doi: 10.1097/CAD.0000000000000833.
There is growing evidence shown that microRNAs (miRNAs) are associated with cancer and can play a role in human cancers as oncogenes or tumor suppressor genes. miRNA-574-5p is a candidate oncogene in various types of cancer, but little is known about biological functions of miR-574-5p in esophageal squamous cell carcinoma (ESCC). In this study, we observe that the expression of miR-574-5p is not only increased in human ESCC tissues but also remarkably increased in cell lines correlates with ZNF70. In vitro, we explored the role of miR-574-5p in ESCC progression via transfection of the miR-574-5p inhibitor into ECA-109 cells. The results show miR-574-5p serve as a tumor promoter regulating cells proliferation and apoptosis in ESCC through mitochondrial-mediated reactive oxygen species (ROS) generation and MAPK pathways. Furthermore, ZNF70 has been proved to as a functional target for miR-574-5p to regulate cells poliferation and apoptosis. In summary, these results suggest that miR-574-5p serves as tumor promoter to promote proliferation and inhibit apoptosis of ESCC cells by targeting ZNF70 via mitochondrial-mediated ROS generation and MAPK pathways. The miR-574-5p/ZNF70 pathway provides a new insight into the molecular mechanisms that the occurrence and development of ESCC and it provides a novel therapeutic target for ESCC.
越来越多的证据表明,microRNAs(miRNAs)与癌症有关,并且可以作为癌基因或肿瘤抑制基因在人类癌症中发挥作用。miRNA-574-5p 是多种类型癌症中的候选癌基因,但关于 miR-574-5p 在食管鳞状细胞癌(ESCC)中的生物学功能知之甚少。在这项研究中,我们观察到 miR-574-5p 的表达不仅在人 ESCC 组织中增加,而且在与 ZNF70 相关的细胞系中也显著增加。在体外,我们通过转染 miR-574-5p 抑制剂到 ECA-109 细胞中来探索 miR-574-5p 在 ESCC 进展中的作用。结果表明,miR-574-5p 通过线粒体介导的活性氧(ROS)生成和 MAPK 途径作为肿瘤促进物调节 ESCC 中的细胞增殖和凋亡。此外,已经证明 ZNF70 是 miR-574-5p 的功能靶标,通过线粒体介导的 ROS 生成和 MAPK 途径调节细胞增殖和凋亡。总之,这些结果表明,miR-574-5p 通过靶向 ZNF70 作为肿瘤促进物,通过线粒体介导的 ROS 生成和 MAPK 途径促进 ESCC 细胞的增殖和抑制凋亡。miR-574-5p/ZNF70 通路为 ESCC 的发生和发展的分子机制提供了新的见解,并为 ESCC 提供了新的治疗靶点。