Molecular Mechanisms Underlying Hepatocellular Carcinoma Induction by Aberrant NRF2 Activation-Mediated Transcription Networks: Interaction of NRF2-KEAP1 Controls the Fate of Hepatocarcinogenesis

International Journal of Molecular Sciences - Tập 21 Số 15 - Trang 5378
Effi Haque1, Md. Rezaul Karim2, Aamir Salam Teeli1, Magdalena Śmiech1, Paweł Leszczyński1, Dawid Winiarczyk1, Emil D. Parvanov3, Atanas G. Atanasov4,1,5,6, Hiroaki Taniguchi1
1Institute of Genetics and Animal Biotechnology of the Polish Academy of Sciences, 05-552 Jastrzębiec, Poland
2Department of Biotechnology and Genetic Engineering, Jahangirnagar University, Savar, Dhaka 1342, Bangladesh
3Division BIOCEV, Institute of Molecular Genetics, Academy of Sciences of the Czech Republic, 420 Prague, Czech Republic
4Department of Pharmacognosy, University of Vienna, 1090 Vienna, Austria
5Institute of Neurobiology, Bulgarian Academy of Sciences, 1113 Sofia, Bulgaria
6Ludwig Boltzmann Institute for Digital Health and Patient Safety, Medical University of Vienna, 1090 Vienna, Austria

Tóm tắt

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.

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Tài liệu tham khảo

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