A new microRNA signal pathway regulated by long noncoding RNA TGFB2-OT1 in autophagy and inflammation of vascular endothelial cells

摘要: TGFB2-OT1 (TGFB2 overlapping transcript 1) is a newly discovered long noncoding RNA (lncRNA) derived from the 3'UTR of TGFB2. It can regulate autophagy in vascular endothelial cells (VECs). However, mechanisms action are unclear, and whether it involved VECs dysfunction needs investigation. Here, level was markedly increased by lipopolysaccharide oxidized low-density lipoprotein, 2 inflammation triggers. A chemical small molecule, 3-benzyl-5-((2-nitrophenoxy) methyl)-dihydrofuran-2(3H)-one (3BDO) significantly decreased levels inhibited effect LPS oxLDL. The NUPR1 upregulated inducers modulated promoting expression TIA1, responsible for processing. We focused on how regulated inflammation. Use miRNA chip assay, overexpression technology 3BDO revealed that 3 microRNAs, MIR3960, MIR4488 MIR4459. Further studies confirmed acted as competing endogenous RNA, bound to MIR4459, then targets CERS1 (ceramide synthase 1), NAT8L (N-acetyltransferase 8-like [GCN5-related, putative]), LARP1 (La ribonucleoprotein domain family, member 1). participate affecting mitochondrial function. level, which promoted SQSTM1 (sequestosome expression, NFKB RELA CASP1 activation, production IL6, IL8 IL1B VECs. Thus, TIA1 may control TGFB2-OT1, targeted CERS1, NAT8L, LARP1, respectively, key proteins