解旋酶
DNA修复
生物
DNA损伤
细胞周期
RecQ解旋酶
端粒
早衰
沃纳综合征
白血病
基因敲除
癌症研究
基因组不稳定性
细胞生物学
K562细胞
癌细胞
遗传学
癌症
细胞培养
DNA
基因
核糖核酸
作者
Xudong Cui,Jing Hou,Shimei Wang,Jia Yu,Sha Cheng,Li Yu,Fa-Jun Song,Heng Luo
标识
DOI:10.1016/j.ijbiomac.2023.128305
摘要
Leukemia is a type of malignant hematological disease that is generally resistant to chemotherapy and has poor therapeutic outcomes. Werner (WRN) DNA helicase, an important member of the RecQ family of helicases, plays an important role in DNA repair and telomere stability maintenance. WRN gene dysfunction leads to premature aging and predisposes humans to various types of cancers. However, the biological function of WRN in cancer remains unknown. In this study, the expression of this RecQ family helicase was investigated in different types of leukemia cells, and the leukemia cell line K562 with high WRN expression was selected to construct a WRN knockdown cell line. The results showed that WRN knockdown inhibited leukemia occurrence and development by regulating the proliferation, cell cycle, differentiation, and aging of cells and other biological processes. The results of transcriptome sequencing revealed that WRN promoted the sensitivity of leukemia cells to the DNA damage inducer Etoposide by regulating cell cycle-related proteins, such as CDC2, cyclin B1, p16, and p21, as well as key proteins in DNA damage repair pathways, such as p53, RAD50, RAD51, and MER11. Our findings show that WRN helicase is a promising potential target for leukemia treatment, providing new ideas for the development of targeted drugs against leukemia.
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