PIWIL1/piRNA-DQ593109 Regulates the Permeability of the Blood-Tumor Barrier via the MEG3/miR-330-5p/RUNX3 Axis

PIWIL1/piRNA-DQ593109 Regulates the Permeability of the Blood-Tumor Barrier via the MEG3/miR-330-5p/RUNX3 Axis

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The blood-tumor barrier (BTB) restricts the efficient delivery of anti-glioma drugs to cranial glioma tissues.Increased BTB permeability may allow greater delivery of the therapeutic agents.Increasing evidence has revealed that PIWI proteins and PIWI-interacting RNAs (piRNAs) play an important role in tumor progression.However, whether PIWI proteins and piRNAs regulate BTB Jeans permeability remains unclear.In the present study, we demonstrated that the PIWIL1/piRNA-DQ593109 (piR-DQ593109) complex was the predominant regulator of BTB permeability.

Briefly, PIWIL1 was upregulated in glioma endothelial cells (GECs).Furthermore, piR-DQ593109 was also overexpressed in GECs, as revealed via a piRNA microarray.Downregulation of PIWIL1 or piR-DQ593109 increased the permeability of the BTB.Moreover, PIWIL1 and piR-DQ593109, which formed a piRNA-induced 12n/1200 wella silencing complex, degraded the long non-coding RNA maternally expressed 3 (MEG3) in a sequenced-dependent manner.Furthermore, restoring MEG3 released post-transcriptional inhibition of Runt related transcription factor 3 (RUNX3) by sponging miR-330-5p.

In addition, RUNX3 bounded to the promoter regions and reduced the promoter activities of ZO-1, occludin, and claudin-5, which significantly impaired the expression levels of ZO-1, occludin, and claudin-5.In conclusion, downregulating PIWIL1 and piR-DQ593109 increased BTB permeability through the MEG3/miR-330-5p/RUNX3 axis.These data may provide insight into glioma treatment.