Crosstalk between NRF2 and Dicer through metastasis regulating MicroRNAs; mir-34a, mir-200 family and mir-103/107 family.

Oxidative stress due to generation of reactive oxygen species (ROS) can cause damage to cellular proteins, lipids and DNA, which is one of crucial causes responsible for cancer. Nuclear factor erythroid 2 [NF-E2]-related factor 2 (NRF2) is a transcription factor of a variety of antioxidant and cytoprotective enzymes, so that it reduces the levels of damaging ROS in the cell. Over expression of NRF2 in cancer cells can enhance cancer progression, confer resistance to chemo and radiotherapy, and metastasis through the process of epithelial-to mesenchymal transition (EMT); which is a hallmark of cancer-related death. Dicer, a key component of the microRNAs biogenesis, is a ribonuclease enzyme which involves in maturation of microRNAs that have a role in distinct steps of metastasis cascade. Moreover, Dicer was found to be regulated by ROS/NRF2 interaction to contribute to activation of DNA damage repair mechanism. In addition, Dicer is directly reduced by mir-103/107 family that confers migratory capacity through down-regulation of mir-200 family (mir-200b/mir-200c/mir-429). Mir-200c and mir-34a were predicted to target the repressor of NRF2; Sirt1. On the other hand, mir-200a and mir-141 (mir-200 family) were detected to regulate NRF2 expression. This review highlights the regulation of redox homeostasis that is mediated by NRF2 could be modulated by metastasis regulating microRNAs under the control of Dicer. In addition, NRF2 may indirectly control DNA damage repair and microRNAs processing machinery through the crosstalk between NRF2 and Dicer. Understanding such interrelations could provide and shed light on the significance of microRNA-based therapies that will improve the action of clinically used cancer treatments.