石蒜碱
细胞周期蛋白依赖激酶1
癌症研究
肝细胞癌
基因敲除
生物
激酶
癌症
药理学
细胞周期
基因
细胞生物学
生物化学
遗传学
植物
生物碱
作者
Shuangshuang Yin,Shenshen Yang,Yanming Luo,Jia Lu,Gaoyong Hu,Kailong Wang,Yingying Shao,Shiyue Zhou,Sangho Koo,Yuling Qiu,Tao Wang,Haiyang Yu
标识
DOI:10.1016/j.bcp.2021.114806
摘要
The pathological changes and possible underlying molecular mechanisms of hepatocellular carcinoma (HCC) are currently unclear. Effective treatment of this pathological state remains a challenge. The purpose of this study is to obtain some key genes with diagnostic and prognostic meaning and to identify potential therapeutic agents for HCC treatment. Here, CDK1, CCNB1 and CCNB2 were found to be highly expressed in HCC patients and accompanied by poor prognosis, and knockdown of them by siRNA drastically induced autophagy and senescence in hepatoma cells. Simultaneously, the anti-HCC effect of lycorine was comparable to that of interfering with these three genes, and lycorine significantly promoted the decrease both in protein and mRNA expression of CDK1. Molecular validation mechanistically demonstrated that lycorine might attenuate the degradation rate of CDK1 via interaction with it, which had been confirmed by cellular thermal shift assay and drug affinity responsive targets stability assay. Taken together, these findings suggested that CDK1, CCNB1 and CCNB2 could be regarded as potential diagnostic and prognostic biomarkers for HCC, and CDK1 might serve as a promising therapeutic target for lycorine against HCC.
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