NRF2 activation induced by PML‐RARα promotes microRNA 125b‐1 expression and confers resistance to chemotherapy in acute promyelocytic leukemia

Analysis of NRF2 in the cytosolic and nuclear fractions indicated that PML-RARα induced constitutive nuclear levels of NRF2 (Figures 1C, 1D, and S1F). [...]PML-RARα could inhibit the degradation of NRF2 (Figure 1E). Because NRF2 signaling is a critical survival pathway that regulates cellular oxidat...

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Veröffentlicht in:Clinical and translational medicine 2021-05, Vol.11 (5), p.e418-n/a
Hauptverfasser: Yu, Xibao, Mansouri, Ardalan, Liu, Zhuandi, Gao, Rili, Li, Kehan, Chen, Cunte, Huang, Youxue, Chen, Zheng, Chen, Shaohua, Lu, Yuhong, Li, Yangqiu, Zeng, Chengwu, Zeng, Yixin
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Sprache:eng
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Zusammenfassung:Analysis of NRF2 in the cytosolic and nuclear fractions indicated that PML-RARα induced constitutive nuclear levels of NRF2 (Figures 1C, 1D, and S1F). [...]PML-RARα could inhibit the degradation of NRF2 (Figure 1E). Because NRF2 signaling is a critical survival pathway that regulates cellular oxidative stress responses,7 we next determined whether ROS levels could be suppressed by NRF2. [...]ChIP assays showed that NRF2 could bind to all four AREs in the miR-125b-1 promoter in these cells (Figure 2E). Because many chemotherapeutic drugs can induce NRF2 nuclear accumulation via oxidative stress,9 we sought to determine whether elevated ROS levels could be responsible for NRF2 activation. SEE PDF] Together, our data demonstrate that miR-125b-1 expression is likely due to PML-RARα-mediated NRF2 activity, thus explaining the elevated miR-125b-1 in primary APL samples. [...]we showed that NRF2/miR-125b-1 plays an important role in ROS detoxification and the resistance to chemotherapy (Figure 4G).
ISSN:2001-1326
2001-1326
DOI:10.1002/ctm2.418