The NQO1/p53/SREBP1 axis promotes hepatocellular carcinoma progression and metastasis by regulating Snail stability.

Xinyue Wang, Ying Liu, Anna Han, Chunxiao Tang, Ran Xu, Linyuan Feng, Yang Yang, Liyan Chen, Zhenhua Lin

Oncogene 2022 Nov

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Hepatocellular carcinoma (HCC) is the second leading cause of cancer-related mortality worldwide, and its abnormal metabolism affects the survival and prognosis of patients. Recent studies have found that NAD(P)H quinone oxidoreductase-1 (NQO1) played an important role in tumor metabolism and malignant progression. However, the molecular mechanisms by which NQO1 regulates lipid metabolism during HCC progression remain unclear. In this study, bioinformatics analysis and immunohistochemical results showed that NQO1 was highly expressed in HCC tissues and its high expression was closely related to the poor prognosis of HCC patients. Overexpression of NQO1 promoted the cell proliferation, epithelial-to-mesenchymal transition (EMT) process, and angiogenesis of HCC cells. Luciferase reporter assay further revealed that NQO1/p53 could induce the transcriptional activity of SREBP1, consequently regulating HCC progression through lipid anabolism. In addition, Snail protein was stabilized by NQO1/p53/SREBP1 axis and triggered the EMT process, and participated in the regulatory role of NQO1/p53/SREBP1 axis in HCC. Together, these data indicated that NQO1/SREBP1 axis promoted the progression and metastasis of HCC, and might be a potential therapeutic target for HCC. © 2022. The Author(s), under exclusive licence to Springer Nature Limited.

Citation

Xinyue Wang, Ying Liu, Anna Han, Chunxiao Tang, Ran Xu, Linyuan Feng, Yang Yang, Liyan Chen, Zhenhua Lin. The NQO1/p53/SREBP1 axis promotes hepatocellular carcinoma progression and metastasis by regulating Snail stability. Oncogene. 2022 Nov;41(47):5107-5120