Canadine抑制HPV-阴性宫颈癌症的上皮-间质转化。

IF 3.6 Q2 MEDICINE, RESEARCH & EXPERIMENTAL Tissue Barriers Pub Date : 2024-07-02 Epub Date: 2023-10-11 DOI:10.1080/21688370.2023.2256641
Yan Ma, Qian-Qian Yang, Dong-Mei Gu, Xiao Yuan, Yu-Hong Wang, Ling-Chuan Guo
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引用次数: 0

摘要

尽管由于HPV疫苗的出现和广泛使用,大多数人口将得到保护,但包括HPV-阴性癌症宫颈癌在内的所有原因的癌症治疗仍值得进一步研究。本研究的重点是Canadine对癌症宫颈上皮间充质转化(EMT)的抑制作用。免疫印迹、伤口愈合和肿瘤侵袭实验表明,低浓度的Canadine可以抑制HT-3细胞(HPV阴性细胞系)的EMT过程、增殖和迁移。结合GEO数据库,发现Canadine可以抑制宫颈肿瘤组织中高表达的几个基因的表达水平,尤其是MAGEA3。进一步的实验证实,Canadine对MAGEA3蛋白的抑制作用随着时间的推移而增加。设计并验证了MAGEA3的小干扰和过表达质粒。在HT-3细胞中,当MAGEA3水平直接降低时,间充质表型标记物降低,上皮表型标记物增加。通过MAGEA3的过表达获得了相反的结果。此外,由于Canadine减少内源性MAGEA3而引起的EMT的抑制也被外源性MAGEA3的过表达所抵消。研究表明,Canadine通过抑制MAGEA3抑制宫颈癌症的EMT。
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Canadine inhibits epithelial mesenchymal transformation of HPV-negative cervical cancer.

Although the majority of the population will be protected due to the advent and widespread use of the HPV vaccine, the treatment of cervical cancer for all causes, including HPV-negative cervical cancer, is still worthy of further research. The focal point of this study was Canadine's inhibition of epithelial-mesenchymal transformation (EMT) in cervical cancer. Immunoblotting, wound healing and tumor invasion experiments showed that low concentration of Canadine could inhibit the EMT process, proliferation and migration of HT-3 cells (HPV-negative cell line). Combined with GEO database, it was found that the expression levels of several genes highly expressed in cervical tumor tissues could be inhibited by Canadine, especially MAGEA3. Further experiments confirmed that the inhibition of Canadine on MAGEA3 protein increased with time. The small interference and overexpression plasmid of MAGEA3 were designed and verified. In HT-3 cells, when MAGEA3 levels were directly decreased, mesenchymal phenotypic markers were decreased and epithelial phenotypic markers were increased. The opposite result was obtained by overexpression of MAGEA3. In addition, the inhibition of EMT due to the reduction of endogenous MAGEA3 by Canadine was also offset by the overexpression of exogenous MAGEA3. The study concludes that Canadine inhibits EMT of cervical cancer by inhibiting MAGEA3.

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来源期刊
Tissue Barriers
Tissue Barriers MEDICINE, RESEARCH & EXPERIMENTAL-
CiteScore
6.60
自引率
6.50%
发文量
25
期刊介绍: Tissue Barriers is the first international interdisciplinary journal that focuses on the architecture, biological roles and regulation of tissue barriers and intercellular junctions. We publish high quality peer-reviewed articles that cover a wide range of topics including structure and functions of the diverse and complex tissue barriers that occur across tissue and cell types, including the molecular composition and dynamics of polarized cell junctions and cell-cell interactions during normal homeostasis, injury and disease state. Tissue barrier formation in regenerative medicine and restoration of tissue and organ function is also of interest. Tissue Barriers publishes several categories of articles including: Original Research Papers, Short Communications, Technical Papers, Reviews, Perspectives and Commentaries, Hypothesis and Meeting Reports. Reviews and Perspectives/Commentaries will typically be invited. We also anticipate to publish special issues that are devoted to rapidly developing or controversial areas of research. Suggestions for topics are welcome. Tissue Barriers objectives: Promote interdisciplinary awareness and collaboration between researchers working with epithelial, epidermal and endothelial barriers and to build a broad and cohesive worldwide community of scientists interesting in this exciting field. Comprehend the enormous complexity of tissue barriers and map cross-talks and interactions between their different cellular and non-cellular components. Highlight the roles of tissue barrier dysfunctions in human diseases. Promote understanding and strategies for restoration of tissue barrier formation and function in regenerative medicine. Accelerate a search for pharmacological enhancers of tissue barriers as potential therapeutic agents. Understand and optimize drug delivery across epithelial and endothelial barriers.
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