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

肿瘤坏死因子-α和白细胞介素-6通过核因子-κB抑制人类脂肪细胞中的microRNA-1275转录

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作者:Yu-Feng Zhou, Zi-Yi Fu, Xiao-Hui Chen, Yan Cui, Chen-Bo Ji, Xi-Rong Guo

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.

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