Down-regulating NQO1 promotes cellular proliferation in K562 cells via elevating DNA synthesis

Publication date: Available online 24 February 2020Source: Life SciencesAuthor(s): Fei-Yan Xiao, Zhi-Ping Jiang, Fang Yuan, Fang-Jiao Zhou, Wei Kuang, Gan Zhou, Xiao-Ping Chen, Rong Liu, Hong-Hao Zhou, Xie-Lan Zhao, Shan CaoAbstractBackgroundNQO1 protein acts as a cellular protective system, on account of its role as a quinone reductase and redox regulator. Nonetheless, new NQO1 roles are emerging—including its regulation of the cellular proliferation of many tumor cells—and this enzyme has been found to relate to the incidence of various diseases, including chronic myeloid leukemia. However, the mechanisms through which NQO1 influences leukemia progression remain unclear.Martial and methodsThe current study looks to name NQO1 as a novel molecular target that modulates DNA synthesis and chronic myeloid leukemia growth.Results and conclusionOur results indicate that the frequency of the T allele of NQO1 polymorphism in chronic myeloid leukemia patients is higher than that among healthy East Asian individuals (0.492 vs. 0.419) and much higher than the average level of the general population (0.492 vs. 0.289) (1000 Genomes). Functionally, NQO1 knockdown increases the protein expression of the TOP2A and MCM complex, and consequently promotes DNA synthesis and K562 cell growth. NQO1 knockdown also promotes tumorigenesis in a xenograft model. NQO1 overexpression, on the other hand, was found to have the opposite effects.SignificanceOur results show that NQO1 downregulation prom...
Source: Life Sciences - Category: Biology Source Type: research