Tumor necrosis factor-α and interleukin-6 suppress microRNA-1275 transcription in human adipocytes through nuclear factor-κB

Abstract

Obesity is a confirmed risk factor for hyperlipidemia, type-II diabetes, hypertension, and cardiovascular disease. MicroRNAs (miRs) have emerged as an important field of study within energy metabolism and obesity. A previous study demonstrated MIR-1275 to be markedly down-regulated during maturation of human preadipocytes. It has been reported that MIR-1275 dysregulates expression in several types of cancer and infections. Little is currently known about the regulation of MIR-1275 transcription. The aim of the current study was to explore the mechanism underlying the expression of MIR-1275 in mature human adipocytes. After differentiation, human adipocytes were incubated with tumor necrosis factor (TNF)-α and interleukin-6. The results of reverse transcription-quantitative polymerase chain reaction demonstrated that MIR-1275 can be down-regulated by TNF-α and IL-6, in human mature adipocytes. Bioinformatic analysis was used to predict nuclear factor (NF)-κB binding sites of MIR-1275's promoter region. Luciferase assay and rescue experiments were performed in HEK293T cells. NF-κB was involved in regulating MIR-1275 transcription by binding to its promoter. In response to TNF-α, NF-κB was bound to the promoter of MIR-1275 and inhibited its transcription. These results indicated that inflammatory factors could regulate MIR-1275 transcription through NF-κB and influencing MIR-1275 effects on obesity.