TARBP2-stablized SNHG7 regulates blood-brain barrier permeability by acting as a competing endogenous RNA to miR-17-5p/NFATC3 in Aβ-microenvironment

Breakdown of blood-brain barrier (BBB) is recognized as serious pathological marker of Alzheimer's disease development. Studies confirmed that beta-amyloid (A beta) deposition induced high BBB permeability by disrupting tight junction (TJ) proteins formed from endothelial cells (ECs). Here, we found TARBP2, SNHG7 and NFATC3 in expressions were increased and miR-17-5p expression was decreased in A beta(1-42)-incubated ECs. Overexpression of TARBP2, SNHG7 and NFATC3 elevated BBB permeability and knockdown of them had converse results. Agomir-17-5p decreased BBB permeability and antagomir-17-5p increased BBB permeability. TARBP2 as a RNA-binding protein (RBP) bound to SNHG7 and resulted in longer half-life of SNHG7. The decreased expression of miR-17-5p had a negative post-transcriptional regulation to NFATC3, leading to the increased expression of NFATC3. In addition, SNHG7 regulated NFATC3 expression by acting as a molecule sponge targeting to miR-17-5p. NFATC3 inhibited TJ proteins expression by functioning as a transcription factor. TARBP2/SNHG7/miR-17-5p/NFATC3 pathway implied a potential mechanism in studies of BBB changes in AD pathological progression.

Automated summary

Breakdown of the blood-brain barrier (BBB) is an important pathological marker in the development of Alzheimer's disease. Beta-amyloid deposition disrupts tight junction proteins formed by endothelial cells, leading to increased BBB permeability. Through regulation of various genes and molecules, the TARBP2/SNHG7/miR-17-5p/NFATC3 pathway may provide insights into the changes in the BBB during the progression of Alzheimer's disease.