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 by researchers from Chongqing Academy of Animal Science 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 (20ng/mL) rapidly activated NF-κB and induced moderate apoptosis. Pyrrolidinedithiocarbamic acid (PDTC, 60µM), a specific NF-κB inhibitor, abated NF-κB activation that rendered the adipocytes vulnerable to TNFα-induced apoptosis. Dozens of miRNAs exhibited significant expression changes following TNFα treatment and the addition of PDTC. MiRNA Microarray profiling indicated 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.

 

Reference
R. Qi, J. Huang, Q. Wang, H. Liu, R. Wang, J. Wang, F. Yang (2017) MicroRNA-224-5p regulates adipocyte apoptosis induced by TNFα via controlling NF-κB activation J. of Cell Phys. doi: 10.1002/jcp.25992 [abstract]

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