Tumor necrosis factor (TNF) α can induce cell apoptosis and activate nuclear transcription (NF)‐κB in different cell types. Activated NF‐κB further promotes or suppresses cellular apoptosis in different cases. A recent study explored the effect of activated NF‐κB on adipocyte apoptosis induced by TNFα and which microRNAs (miRNAs) were involved in the process.

Their findings demonstrated that treatment of differentiated 3T3‐L1 adipocytes with TNFα (20 ng/mL) rapidly activated NF‐κB and induced moderate apoptosis. Pyrrolidinedithiocarbamic acid (PDTC, 60 µM), a specific NF‐κB inhibitor, abated NF‐κB activation that rendered the adipocytes vulnerable to TNFα‐induced apoptosis. MiRNA microarray profiling showed that dozens of miRNAs exhibit significant expression changes following TNFα treatment and the addition of PDTC. In which, miRNA‐224‐5p (miR‐224) was up‐regulated by TNFα exposure but down‐regulated by PDTC addition. Furthermore, over‐expression of miR‐224 promoted NF‐κB activation and prevented the adipocyte apoptosis induced by TNFα, while miR‐224 deficiency showed the opposite effects. The TRAF‐associated NF‐κB activator (TANK) gene was identified as a direct target of miR‐224 by computational and luciferase reporter assays. Additionally, silencing the TANK gene by the small interfering RNA similarly promoted NF‐κB activation and attenuated the cellular apoptosis.

In conclusion, these findings demonstrate that miR‐224 plays an essential role in adipocyte apoptosis caused by TNFα through control of NF‐κB activation via targeting the TANK gene.

 

Changes in miRNAs expression followed NF‐κB activation by TNFα or suppression by PDTC in 3T3‐L1 adipocytes. (a) Clustering map of 45 differentially expressed miRNAs following TNFα treatment (p < 0.01). Red indicates the level of miRNA expression is higher than the median, and green indicates that the level is lower than the median. (b) Clustering map of 10 miRNAs with significant expression changes between PDTC + TNFα treated cells versus TNFα treated cells (p < 0.01). (c) Volcano Plot of the 36 differentially expressed miRNAs. Red indicates p < 0.05. (d) Relative expression levels of miR‐224 from the qRT‐PCR results

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Reference
R. Qi, J. Huang, Q. Wang, H. Liu, R. Wang, J. Wang, F. Yang (2017) MicroRNA2245p regulates adipocyte apoptosis induced by TNFα via controlling NFκB activation Cellular Physiology doi: 10.1002/jcp.25992 [abstract]

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