Z-DNA, a well-known non-canonical form of DNA involved in gene regulation, is often found in gene promoters. Transposable elements (TEs), which make up 45% of the human genome, can move from one location to another within the genome. TEs play various biological roles in host organisms, and like Z-DNA, can influence transcriptional regulation near promoter regions. MicroRNAs (miRNAs) are a class of small non-coding RNA molecules that play a critical role in the regulation of gene expression. Although TEs can generate Z-DNA and miRNAs can bind to Z-DNA, how these factors affect gene transcription has yet to be elucidated. Here, we identified potential Z-DNA forming sequences (ZFSs), including TE-derived ZFS, in the promoter of prostaglandin reductase 1 (PTGR1) by data analysis. The transcriptional activity of these ZFSs in PTGR1 was confirmed using dual-luciferase reporter assays. In addition, we discovered a novel ZFS binding miRNA (miR-6867-5p) that suppressed PTGR1 expression by targeting to ZFSs. In conclusion, these findings suggest that TEs can regulate PTGR1 gene expression by forming Z-DNA and that miR-6867-5p can suppress PTGR1 by interacting with ZFSs.

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