NF-E2-related factor 2 (NRF2) is a basic leucine zipper transcription factor, a master regulator of redox homeostasis regulating a variety of genes for antioxidant and detoxification enzymes. NRF2 was, therefore, initially thought to protect the liver from oxidative stress. Recent studies, however, have revealed that mutations in NRF2 cause aberrant accumulation of NRF2 in the nucleus and exert the upregulation of NRF2 target genes. Moreover, among all molecular changes in hepatocellular carcinoma (HCC), NRF2 activation has been revealed as a more prominent pathway contributing to the progression of precancerous lesions to malignancy. Nevertheless, how its activation leads to poor prognosis in HCC patients remains unclear. In this review, we provide an overview of how aberrant activation of NRF2 triggers HCC development. We also summarize the emerging roles of other NRF family members in liver cancer development.

Department of Biotechnology and Genetic Engineering Jahangirnagar University Savar Dhaka 1342 Bangladesh

Department of Pharmacognosy University of Vienna 1090 Vienna Austria

Division BIOCEV Institute of Molecular Genetics Academy of Sciences of the Czech Republic 420 Prague Czech Republic

Institute of Genetics and Animal Biotechnology of the Polish Academy of Sciences 05 552 Jastrzębiec Poland

Institute of Neurobiology Bulgarian Academy of Sciences 1113 Sofia Bulgaria

Ludwig Boltzmann Institute for Digital Health and Patient Safety Medical University of Vienna 1090 Vienna Austria

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