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Chondroitin polymerizing factor (CHPF) promotes development of malignant melanoma through regulation of CDK1.
Cell Death & Disease ( IF 9 ) Pub Date : 2020-07-01 , DOI: 10.1038/s41419-020-2526-9
Wei Sun 1, 2 , Fang Zhao 3 , Yu Xu 1, 2 , Kai Huang 4 , Xianling Guo 5, 6, 7 , Biqiang Zheng 1, 2 , Xin Liu 8 , Zhiguo Luo 8 , Yunyi Kong 9 , Midie Xu 9 , Dirk Schadendorf 3 , Yong Chen 1
Affiliation  

Chondroitin polymerizing factor (CHPF) is an important member of glycosyltransferases involved in the biosynthesis of chondroitin sulfate (CS). However, the relationship between CHPF and malignant melanoma (MM) is still unknown. In this study, it was demonstrated that CHPF was up-regulated in MM tissues compared with the adjacent normal skin tissues and its high expression was correlated with more advanced T stage. Further investigations indicated that the over-expression/knockdown of CHPF could promote/inhibit proliferation, colony formation and migration of MM cells, while inhibiting/promoting cell apoptosis. Moreover, knockdown of CHPF could also suppress tumorigenicity of MM cells in vivo. RNA-sequencing followed by Ingenuity pathway analysis (IPA) was performed for exploring downstream of CHPF and identified CDK1 as the potential target. Furthermore, our study revealed that knockdown of CDK1 could inhibit development of MM in vitro, and alleviate the CHPF over-expression induced promotion of MM. In conclusion, our study showed, as the first time, CHPF as a tumor promotor for MM, whose function was carried out probably through the regulation of CDK1.



中文翻译:

软骨素聚合因子(CHPF)通过调节CDK1促进恶性黑色素瘤的发展。

软骨素聚合因子(CHPF)是参与硫酸软骨素(CS)生物合成的糖基转移酶的重要成员。但是,CHPF与恶性黑色素瘤(MM)之间的关系仍然未知。在这项研究中,已证明与相邻的正常皮肤组织相比,MM组织中的CHPF上调,并且其高表达与更晚期的T期相关。进一步的研究表明,CHPF的过度表达/抑制可促进/抑制MM细胞的增殖,集落形成和迁移,同时抑制/促进细胞凋亡。此外,敲低CHPF还可以在体内抑制MM细胞的致瘤性。进行RNA测序,然后进行智能路径分析(IPA),以探索CHPF的下游并将CDK1鉴定为潜在靶标。此外,我们的研究表明,敲除CDK1可以在体外抑制MM的发展,并减轻CHPF过表达诱导的MM促进。总之,我们的研究首次显示CHPF作为MM的肿瘤促进剂,其功能可能是通过调节CDK1来实现的。

更新日期:2020-07-01
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