Journal
MOLECULAR AND CELLULAR BIOCHEMISTRY
Volume 477, Issue 1, Pages 191-203Publisher
SPRINGER
DOI: 10.1007/s11010-021-04269-0
Keywords
NAFLD; Acetylation; lncRNA NEAT1; GRIA3; miR-212-5p
Categories
Funding
- Fund Project of University of South China for Prevention and Control of COVID-19 [2020-22]
- Scientific Research Fund Project of Hunan Provincial Health Commission [20201983]
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Non-alcoholic fatty liver disease (NAFLD) is a global health burden, and the regulatory mechanisms involving H3K27 acetylation, lncRNA NEAT1, miR-212-5p, and GRIA3 in NAFLD were investigated. Upregulation of NEAT1 and GRIA3, and downregulation of miR-212-5p were observed in NAFLD patients. Fatty acid treatment promoted NEAT1 and GRIA3 expression, suppressed miR-212-5p expression, and led to lipid accumulation.
Non-alcoholic fatty liver disease (NAFLD) was a world-wide health burden. H3K27 acetylation, long non-coding RNA (lncRNA), and miRNA were all implicated in NAFLD regulation, yet the detailed regulatory mechanism was not well understood. LncRNA NEAT1, miR-212-5p, and GRIA3 expression were detected both in high fatty acid-treated hepatocytes cells and NAFLD patients. Lipid droplets were stained and analyzed by oil red O staining. Expression of fatty acid synthase (FASN), acetyl-CoA carboxylase (ACC), and GRIA3 was detected by qRT-PCR and western blot. RNA level of lncRNA NEAT1 and miR-212-5p was analyzed by qRT-PCR. The binding sequences of lncRNA NEAT1/miR-212-5p and miR-212-5p/GRIA3 were predicted bioinformatically and validated through luciferase assay. ChIP was performed to analyze H3K27 acetylation on the promoter of lncRNA NEAT1. LncRNA NEAT1 and GRIA3 was upregulated, while miR-212-5p was downregulated in NAFLD patients. FFA promoted lncRNA NEAT1 and GRIA3 expression while suppressing miR-212-5p and promoted lipid accumulation as indicated by increased oil red O staining and FAS and ACC expression. ChIP indicated enrichment of H3K27 on NEAT1 promoter. Inhibition of H3K27 acetylation suppressed lncRNA NEAT1 level. Luciferase results indicated direct interaction of NEAT1/miR-212-5p (which was confirmed by RIP) and miR-212-5p/GRIA3. LncRNA NEAT1 knockdown upregulated miR-212-5p level and inhibited FFA-induced lipid accumulation while suppressing GRIA3 expression. Such function was antagonized by miR-212-5p inhibition and GRIA3 knockdown counteracted with miR-212-5p inhibition. H3K27 acetylation was enriched within the promoter of lncRNA NEAT1 and promoted lncRNA NEAT1 transcription. LncRNA NEAT1 could then interact with miR-212-5p and suppress its cellular concentration.
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