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miRNA-574-5p 通过产生活性氧和 MAPK 通路激活下调 ZNF70 并影响人食管鳞状细胞癌的进展。

miRNA-574-5p downregulates ZNF70 and influences the progression of human esophageal squamous cell carcinoma through reactive oxygen species generation and MAPK pathway activation.

机构信息

Department of chest surgery, The second affiliated hospital of Air Force Military medical University, Xi'an, Shanxi, China.

出版信息

Anticancer Drugs. 2020 Mar;31(3):282-291. doi: 10.1097/CAD.0000000000000833.

Abstract

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.

摘要

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。

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