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. Author manuscript; available in PMC: 2019 Sep 11.
Published in final edited form as: J Environ Sci Health C Environ Carcinog Ecotoxicol Rev. 2019 Jul 15;37(3):180–214. doi: 10.1080/10590501.2019.1639481

Figure 2.

Figure 2.

Diverse mechanisms of miRNA regulation in CYP2E1 expression. (A) Schematic map of CYP2E1 mRNA with miRNA targeting sites. CYP2E1 mRNA is directly targeted by multiple miRNAs at different regions (miR-214–3p at the coding sequence and miR-552, miR-570, and miR-378a-5p at the 3′-UTR) for post-transcriptional gene repression. 3′ end of the miR-570 MRE and 5′ end of the miR-378a-5p MRE on CYP2E1 mRNA overlap and both encompass two SNPs 1556 T/A and 1561 A/G; however, the SNPs only affect miRNA-mediated gene suppression by miR-570 but not miR-378a-5p. (B) Molecular mechanisms of transcriptional and post-transcriptional regulation of CYP2E1 gene expression in the cell. miR-214–3p, miR-552, miR-570, and miR-378a-5p recognize and bind to CYP2E1 mRNA in the cytoplasm for post-transcription gene suppression. miR-552 can also bind to the promoter region of CYP2E1, which prohibits RNA Pol II from interacting with the promoter and thereby inhibit CYP2E1 transcription. MiR-320a and miR-877–5p downregulates CYP2E1 transactivators HNF1A and NR1I2, respectively, by directly binding to the 3′-UTR of the corresponding transactivator; the decrease of HNF1A and NR1I2 leads to reduced transcription of CYP2E1.