Neat1 regulates oxidized low-density lipoprotein-induced inflammation and lipid uptake in macrophages via paraspeckle formation.

Oxidized low-density lipoprotein (oxLDL) indu-ces macrophage inflammation and lipid uptake, and serves important roles in the development of atherosclerosis. The long non-coding RNA (lncRNA) nuclear paraspeckle assembly transcript 1 (neat1) has two isoforms; the longer isoform, neat1_2, mediates the formation of subnuclear structures called paraspeckles. Reverse transcription‑quantitative polymerase chain reaction (RT‑qPCR), western blotting and RNA protein immunoprecipitation (RIP), revealed that oxLDL induced paraspeckle formation in the THP‑1 cell line. Additionally, the nuclear factor‑κB and p38 pathways were observed to be involved in neat1 transcription. To investigate the role of paraspeckles in oxLDL‑induced macrophage inflammation and lipid uptake, macrophages were transfected with small interfering RNAs against NEAT1, NEAT1_2, non‑POU domain-containing octamer-binding (NONO) and splicing factor proline and glutamine rich prior to oxLDL incubation. In addition, inflammation‑associated pathways and scavenger receptors were analyzed by performing western blotting and RT‑qPCR. p65 phosphorylation and cluster of differentiation 36 (CD36) were demonstrated to serve roles in paraspeckle‑mediated inflammation and lipid uptake, respectively. To determine the underlying mechanism, RIP was preformed, which revealed that NONO binds CD36 mRNA to decrease its expression. In conclusion, oxLDL induced neat1_2‑mediated paraspeckle formation. Paraspeckles participate in oxLDL‑induced macrophage inflammation and lipid uptake by regulating p65 phosphorylation and CD36 mRNA.

Pubmed ID: 29257236 RIS Download